Monoklonalna gammapatia o nieokreślonym znaczeniu (mgus)

Monoklonalna gammapatia o nieokreślonym znaczeniu (mgus)
Etiologia i przyczyny

Monoklonalna gammapatia o nieokreślonym znaczeniu (MGUS) to stan przednowotworowy charakteryzujący się obecnością białka monoklonalnego (białka M) produkowanego przez klon komórek plazmatycznych w szpiku kostnym, przy czym odsetek tych komórek jest <10%. MGUS jest bezobjawowy, ale stanowi prekursor chorób limfoproliferacyjnych, takich jak szpiczak mnogi, makroglobulinemia Waldenströma czy amyloidoza. Ryzyko progresji wynosi około 1% rocznie, zależne od poziomu białka M (≥15 g/L), typu immunoglobuliny (IgA wyższe ryzyko niż IgG), stosunku wolnych łańcuchów lekkich, odsetka komórek plazmatycznych (>5%) oraz obecności krążących komórek plazmatycznych. MGUS dzieli się na podtypy: nie-IgM (85% przypadków, ryzyko progresji 0,5-1% rocznie), IgM (15%, ryzyko progresji ~1,5% rocznie) oraz związany z nieprawidłowym stosunkiem wolnych łańcuchów lekkich (ryzyko 0,3% rocznie). Wiek (>50 lat), płeć męska, rasa (wyższe ryzyko u osób pochodzenia afrykańskiego), czynniki genetyczne, środowiskowe (pestycydy, promieniowanie jonizujące) oraz przewlekła stymulacja antygenowa i choroby autoimmunologiczne wpływają na rozwój MGUS.

Etiologia monoklonalnej gammapatii o nieokreślonym znaczeniu (MGUS)

Monoklonalna gammapatia o nieokreślonym znaczeniu (MGUS) jest zaburzeniem przednowotwotowym charakteryzującym się obecnością nieprawidłowego białka monoklonalnego (białka M) we krwi, wytwarzanego przez nieprawidłowy klon komórek plazmatycznych w szpiku kostnym.¹² Chociaż MGUS nie jest nowotworem złośliwym i zwykle nie powoduje objawów, stanowi stan prekursorowy dla wielu chorób limfoproliferacyjnych, w tym szpiczaka mnogiego, makroglobulinemii Waldenströma oraz amyloidozy.³⁴

Nieznane dokładne przyczyny MGUS

Dokładna przyczyna MGUS pozostaje nieznana, mimo intensywnych badań naukowych. Większość ekspertów zgadza się, że rozwój MGUS jest prawdopodobnie wynikiem złożonej interakcji między czynnikami genetycznymi, środowiskowymi i immunologicznymi.⁵⁶ Badacze uważają, że prawdopodobnie te same teorie, które wyjaśniają patogenezę szpiczaka mnogiego, mogą być również istotne w przypadku MGUS.⁷

Ważnym osiągnięciem naukowym było odkrycie, że praktycznie wszystkie przypadki szpiczaka mnogiego są poprzedzone stanem MGUS, co podkreśla kluczową rolę MGUS w progresji do bardziej zaawansowanych chorób limfoproliferacyjnych.⁸⁹

Czynniki genetyczne

Istnieją przekonujące dowody na udział czynników genetycznych w rozwoju MGUS:

Badania populacyjne z północnej Europy i Stanów Zjednoczonych wykazały zwiększone ryzyko MGUS wśród krewnych pierwszego stopnia osób z MGUS lub szpiczakiem, co sugeruje rolę genów podatności dziedzicznej.¹⁰
Osoby z bliskim krewnym (rodzic, rodzeństwo) z MGUS lub szpiczakiem mnogim mają 2-3 razy większe ryzyko rozwoju MGUS.¹¹¹²
W komórkach plazmatycznych pacjentów z MGUS często występują charakterystyczne aberracje chromosomalne podobne do tych obserwowanych w szpiczaku mnogim.¹³
Translokacje chromosomowe dotyczące regionów odpowiedzialnych za komponenty ciężkiego łańcucha immunoglobulin są częste u pacjentów z MGUS.¹⁴

Czynniki środowiskowe

Ekspozycja na różne czynniki środowiskowe może zwiększać ryzyko rozwoju MGUS:

Pestycydy i substancje chemiczne – narażenie na pestycydy (np. aldryna, dieldryna, permetryna) oraz rozpuszczalniki przemysłowe zostało powiązane ze zwiększonym ryzykiem MGUS.¹⁵¹⁶
Promieniowanie jonizujące – ekspozycja na wysokie poziomy promieniowania może zwiększać ryzyko MGUS, co potwierdzają badania przeprowadzone wśród ofiar bomby atomowej w Nagasaki.¹⁷¹⁸
Zawodowa ekspozycja – pracownicy rolni wykazują wyższe ryzyko rozwoju MGUS w wielu badaniach kontrolnych.¹⁹

Infekcje i choroby zapalne

Przewlekła stymulacja antygenowa może odgrywać rolę w patogenezie MGUS:

Przebyte infekcje – zapalenie płuc, zapalenie wątroby, zapalenie opon mózgowych i zakażenie HIV zostały powiązane z większym ryzykiem MGUS.²⁰
Przewlekłe stany zapalne – mogą prowadzić do stymulacji receptora komórki B przez przetrwałe antygeny egzogenne lub endogenne, co może prowadzić do klonalnej proliferacji komórek B i rozwoju MGUS.²¹
Przewlekła stymulacja antygenowa – ekspozycja na antygeny może prowadzić do selekcji klonów komórek B i rozwoju MGUS.²²

Choroby autoimmunologiczne

Związek między chorobami autoimmunologicznymi a MGUS jest złożony:

Choroby autoimmunologiczne są dobrze udokumentowanym czynnikiem ryzyka rozwoju MGUS.²³
MGUS może być związane z zaburzeniami tkanki łącznej, neuropatiami obwodowymi, nabytym niedoborem inhibitora esterazy C1 (obrzęk naczynioruchowy) i chorobami skóry.²⁴
Choroby autoimmunologiczne, takie jak niedokrwistość złośliwa i toczeń, mogą zwiększać ryzyko MGUS.²⁵²⁶
Paradoksalnie, szwedzkie badanie populacyjne wykazało, że pacjenci z historią chorób autoimmunologicznych mają znacznie niższe ryzyko progresji z MGUS do szpiczaka mnogiego lub innych chorób limfoproliferacyjnych.²⁷

Czynniki demograficzne i nieuniknione

Pewne czynniki ryzyka MGUS nie podlegają modyfikacji:

Wiek – częstość występowania MGUS znacząco wzrasta z wiekiem, występując u około 3% białej populacji powyżej 50 roku życia i 5% osób powyżej 70 roku życia.²⁸²⁹
Płeć – MGUS występuje prawie dwukrotnie częściej u mężczyzn niż u kobiet.³⁰³¹
Rasa – częstość występowania MGUS jest wyższa u osób pochodzenia afrykańskiego w porównaniu z osobami rasy białej czy azjatyckiej.³²³³

Czynniki związane ze stylem życia

Pewne aspekty stylu życia mogą również wpływać na ryzyko rozwoju MGUS:

Palenie tytoniu – zostało powiązane ze zwiększonym ryzykiem MGUS w niektórych badaniach.³⁴³⁵
Dieta – niska konsumpcja owoców została zidentyfikowana jako potencjalny czynnik ryzyka MGUS.³⁶ Jednakże, warto zaznaczyć, że nieprawidłowe białka nie są powodowane przez określoną dietę ani przez spożywanie białek pokarmowych.³⁷
Otyłość – BMI powyżej 30 kg/m² zostało powiązane z wyższym ryzykiem MGUS w niektórych badaniach.³⁸

Mechanizmy patogenetyczne w rozwoju MGUS

Rozwój MGUS wiąże się z szeregiem złożonych zmian na poziomie komórkowym i molekularnym:

Nieprawidłowe komórki plazmatyczne

W MGUS dochodzi do klonalnej ekspansji nieprawidłowych komórek plazmatycznych w szpiku kostnym:

Komórki plazmatyczne w MGUS nieprawidłowo odzyskują zdolność do proliferacji, co normalnie nie występuje w dojrzałych komórkach plazmatycznych.³⁹
Klonalna ekspansja prowadzi do nadprodukcji białek monoklonalnych (białka M).⁴⁰
W definicji MGUS, odsetek klonalnych komórek plazmatycznych w szpiku kostnym musi być mniejszy niż 10%.⁴¹

Produkcja białka monoklonalnego

Kluczowym elementem patofizjologii MGUS jest produkcja białka monoklonalnego:

Nieprawidłowe komórki plazmatyczne produkują nieużyteczne przeciwciała (białko M), które nie są ukierunkowane na określone patogeny, więc nie pomagają w zwalczaniu infekcji.⁴²
Białko M może gromadzić się we krwi i moczu.⁴³
Najczęściej MGUS obejmuje populacje komórkowe wytwarzające immunoglobuliny IgG lub IgA.⁴⁴
Poziom białka M w MGUS musi być niższy niż 30 g/L dla rozpoznania.⁴⁵

Zmiany w mikrośrodowisku szpiku kostnego

Mikrośrodowisko szpiku kostnego odgrywa istotną rolę w patogenezie MGUS:

Zaburzenia w mikrośrodowisku szpiku kostnego mogą przyczyniać się do rozwoju i podtrzymywania klonu MGUS.⁴⁶
Interakcje między klonalnymi komórkami plazmatycznymi a innymi komórkami szpiku kostnego mogą sprzyjać przeżyciu i proliferacji nieprawidłowych komórek.⁴⁷

Typy MGUS i ich znaczenie etiologiczne

Wyróżnia się kilka typów MGUS, które różnią się potencjałem progresji do określonych chorób złośliwych:

MGUS nie-IgM (IgG, IgA, IgD)

Jest to najczęstszy podtyp MGUS:

Stanowi około 85% wszystkich przypadków MGUS.⁴⁸
Ma potencjał progresji do tlącego się (bezobjawowego) szpiczaka mnogiego, a następnie do objawowego szpiczaka mnogiego.⁴⁹
Roczne ryzyko progresji wynosi około 0,5-1% rocznie.⁵⁰

MGUS IgM

Ten podtyp stanowi około 15% przypadków MGUS:

Jest rozpatrywany oddzielnie od MGUS nie-IgM, ponieważ ma potencjał progresji do makroglobulinemii Waldenströma i innych chorób limfoproliferacyjnych.⁵¹
Rzadziej może rozwinąć się w chłoniaka lub amyloidozę AL.⁵²
Ryzyko progresji jest wyższe niż w przypadku MGUS nie-IgM i wynosi około 1,5% rocznie.⁵³

MGUS łańcuchów lekkich

Jest to rzadszy podtyp MGUS:

Charakteryzuje się nieprawidłowym stosunkiem wolnych łańcuchów lekkich w surowicy.⁵⁴
Może prowadzić do szpiczaka łańcuchów lekkich.⁵⁵
Ma najniższe ryzyko progresji spośród wszystkich typów MGUS, wynoszące około 0,3% rocznie.⁵⁶⁵⁷

Czynniki ryzyka progresji MGUS do chorób złośliwych

Progresja MGUS do szpiczaka mnogiego lub innych chorób limfoproliferacyjnych nie jest jednakowa dla wszystkich pacjentów i zależy od wielu czynników:

Czynniki biologiczne wpływające na progresję

Stężenie białka M – poziom białka monoklonalnego ≥15 g/L jest najważniejszym czynnikiem determinującym progresję.⁵⁸⁵⁹
Typ immunoglobuliny – izotyp IgA wiąże się z wyższym ryzykiem progresji niż IgG.⁶⁰
Nieprawidłowy stosunek wolnych łańcuchów lekkich w surowicy zwiększa ryzyko progresji.⁶¹
Odsetek komórek plazmatycznych w szpiku kostnym – wartość >5% zwiększa ryzyko progresji.⁶²
Redukcja obu nieuwikłanych izotypów immunoglobulin jest negatywnym czynnikiem prognostycznym.⁶³
Krążące komórki plazmatyczne we krwi obwodowej.⁶⁴

Skumulowane ryzyko progresji

Ryzyko progresji MGUS do bardziej zaawansowanych chorób kumuluje się w czasie:

Średnie ryzyko progresji wynosi około 1% rocznie, co oznacza, że u 1-2 osób ze 100 z MGUS rocznie rozwinie się nowotwór z MGUS.⁶⁵
Ryzyko pozostaje stałe przez całe życie pacjenta.⁶⁶
Pacjenci z MGUS, którzy mają nieprawidłowy stosunek wolnych łańcuchów lekkich w surowicy, MGUS nie-IgG i wysokie stężenie białka M (≥1,5 g/dL), mają 58% bezwzględne ryzyko rozwoju szpiczaka po 20 latach obserwacji.⁶⁷
Dla porównania, pacjenci z MGUS bez żadnego z tych czynników ryzyka mają tylko 5% bezwzględne ryzyko progresji do szpiczaka po 20 latach.⁶⁸

Dynamika ryzyka progresji

Najnowsze badania wskazują, że ryzyko progresji MGUS może zmieniać się w czasie:

Wcześniejsze zalecenia zakładały, że ryzyko progresji pozostaje stałe, jednak nowsze dane sugerują, że może się ono zmieniać.⁶⁹
MGUS o niskim i pośrednim ryzyku może przekształcić się w MGUS wysokiego ryzyka w ciągu kilku lat.⁷⁰
To odkrycie wspiera coroczne badania krwi dla wszystkich osób z rozpoznaniem MGUS oraz coroczną ocenę klinicznego statusu ryzyka pacjenta.⁷¹

Monoklonalna gammapatia o znaczeniu nerkowym (MGRS)

Specjalnym wariantem MGUS jest monoklonalna gammapatia o znaczeniu nerkowym (MGRS), która prowadzi do uszkodzenia nerek:

MGRS odnosi się do sytuacji, gdy niewielki klon komórek plazmatycznych, który nie spełnia kryteriów szpiczaka, powoduje uszkodzenie nerek poprzez wytwarzanie toksycznego białka monoklonalnego.⁷²⁷³
Uszkodzenie nerek może obejmować chorobę depozytową immunoglobulin monoklonalnych (MIDD), w tym chorobę depozytową łańcuchów lekkich (LCDD), chorobę depozytową łańcuchów ciężkich (HCDD) oraz chorobę depozytową łańcuchów lekkich i ciężkich (LHCDD).⁷⁴
Choroby nerek związane z białkiem M mają wysoki wskaźnik nawrotów po przeszczepieniu nerki.⁷⁵
Termin MGRS został zaproponowany dla tych patologicznych stanów, aby odróżnić je od bezobjawowego MGUS.⁷⁶

Podsumowanie przyczyn i czynników ryzyka MGUS

Etiologia MGUS jest wieloczynnikowa i złożona, obejmująca interakcję między predyspozycjami genetycznymi, czynnikami środowiskowymi i zaburzeniami immunologicznymi:

MGUS jest najprawdopodobniej wynikiem genetycznych aberracji w komórkach plazmatycznych, które mogą być wyzwalane przez przewlekłą stymulację antygenową, czynniki środowiskowe lub choroby autoimmunologiczne.⁷⁷
Czynniki demograficzne, takie jak wiek powyżej 50 lat, płeć męska i pochodzenie afrykańskie, znacząco zwiększają ryzyko MGUS.⁷⁸
Ekspozycja środowiskowa na pestycydy, rozpuszczalniki i promieniowanie jonizujące może przyczyniać się do rozwoju MGUS.⁷⁹
Przewlekłe infekcje, stany zapalne i choroby autoimmunologiczne mogą stanowić podłoże dla rozwoju MGUS poprzez stymulację antygenową.⁸⁰
Historia rodzinna MGUS lub szpiczaka mnogiego zwiększa ryzyko rozwoju MGUS, sugerując komponent genetyczny w etiologii.⁸¹

Zrozumienie etiologii i czynników ryzyka MGUS jest kluczowe dla opracowania strategii profilaktycznych i terapeutycznych dla tej choroby oraz związanych z nią schorzeń limfoproliferacyjnych. Mimo że MGUS samo w sobie jest stanem łagodnym, jego potencjał do progresji do bardziej złośliwych chorób, takich jak szpiczak mnogi, sprawia, że dokładna diagnostyka i regularne monitorowanie są niezbędne dla optymalnego zarządzania pacjentami.⁸²⁸³

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Materiały źródłowe

#1 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK507880/
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] No specific cause of non-IgM MGUS has been identified. However, the disease may be associated with some non-malignant disorders such as connective tissue disorders, peripheral neuropathies, dermatological diseases such as acquired C1 esterase inhibitor deficiency (angioedema), endocrine diseases, and liver infections such as hepatitis C virus infection and HIV liver disease. […] Population-based studies from northern Europe and the United States show increased risk of MGUS among first-degree relatives of those with MGUS or myeloma, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
#2 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate
https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance
Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. […] MGUS occurs in over 3 percent of the White population over the age of 50 and is typically detected as an incidental finding when individuals undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders (eg, peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, or elevated erythrocyte sedimentation rate). […] There are three distinct clinical types of MGUS, each with a risk of progressing through a unique intermediate (more advanced) premalignant stage and then to a malignant plasma cell dyscrasia or lymphoproliferative disorder: […] Non-IgM MGUS (IgG, IgA, or IgD MGUS) â Non-IgM MGUS is the most common subtype of MGUS and has the potential to progress to smoldering (asymptomatic) multiple myeloma and to symptomatic multiple myeloma.
#3 Monoclonal gammopathy of undetermined significance – Wikipedia
https://en.wikipedia.org/wiki/Monoclonal_gammopathy_of_undetermined_significance
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is usually found during standard laboratory blood or urine tests. […] The progression from MGUS to multiple myeloma usually involves several steps. […] At the Mayo Clinic, MGUS transformed into multiple myeloma or similar lymphoproliferative disorders at the rate of about 0.52% a year depending on risk category. […] In 2009, prospective data demonstrated that all or almost all cases of multiple myeloma are preceded by MGUS. […] In addition to multiple myeloma, MGUS may also progress to Waldenstrm’s macroglobulinemia or primary amyloidosis.
#4 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate
https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance
IgM MGUS â IgM MGUS accounts for approximately 15 percent of MGUS cases. It is considered separately from the non-IgM MGUS because it has the potential to progress to smoldering WaldenstrÃ¶ m macroglobulinemia and to symptomatic WaldenstrÃ¶ m macroglobulinemia, and less often to lymphoma or AL amyloidosis. Infrequently, IgM MGUS can progress to IgM multiple myeloma.
#5 Monoclonal Gammopathy of Undetermined Significance (MGUS)
https://www.healthline.com/health/how-serious-is-mgus
Monoclonal gammopathy of undetermined significance (MGUS) is an abnormal finding of a blood test. It means theres a specific protein present in your blood and is an early sign of certain types of a cancer called myeloma. […] Doctors and scientists arent sure exactly what causes MGUS. Its thought that certain genetic changes and environmental factors may affect whether a person develops this condition. […] What doctors do know is that MGUS causes abnormal plasma cells in the bone marrow to produce M protein. […] The prevalence of MGUS is twice as high in African Americans when compared with white Americans. This is most likely be due to genetic factors. Environmental factors are possible, but evidence is lacking. […] Studies indicate that people with a first-degree relative with MGUS or multiple myeloma have a 2 to 3 times higher risk of developing MGUS. A first-degree relative is a full sibling or biological parent. […] Studies have also found that a family history of multiple myeloma is associated with a 2 to 4 times increased risk of developing multiple myeloma.
#6 Monoclonal gammopathy of undetermined significance (MGUS) | Altru Health System
https://www.altru.org/health-library/conditions/monoclonal-gammopathy-of-undetermined-significance-mgus
Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an atypical protein is found in the blood. […] Experts don’t know what causes MGUS. Changes in genes and being around certain chemicals, such as those used to kill pests, appear to play a role.
#7 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. The cause of MGUS is unknown, though the same theories that apply to the pathogenesis of MM may be valid in MGUS. […] Risk factors for MGUS have been identified. Nonmodifiable risk factors include the following: Older age, Male sex, Black race, Family history of MGUS and related diseases. […] Other risk factors include the following: Specific prior infections (eg, pneumonia, hepatitis, meningitis, HIV), Inflammatory disorders, Autoimmune disease, Smoking, Pesticide exposure (eg, aldrin, dieldrin, permethrin). […] Most cases of MGUS involve IgG or IgA monoclonal cell populations. […] Several studies have confirmed that characteristic genetic abnormalities of MM are present in patients with MGUS.
#8 Monoclonal gammopathy of undetermined significance – Wikipedia
https://en.wikipedia.org/wiki/Monoclonal_gammopathy_of_undetermined_significance
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is usually found during standard laboratory blood or urine tests. […] The progression from MGUS to multiple myeloma usually involves several steps. […] At the Mayo Clinic, MGUS transformed into multiple myeloma or similar lymphoproliferative disorders at the rate of about 0.52% a year depending on risk category. […] In 2009, prospective data demonstrated that all or almost all cases of multiple myeloma are preceded by MGUS. […] In addition to multiple myeloma, MGUS may also progress to Waldenstrm’s macroglobulinemia or primary amyloidosis.
#9
https://haematologica.org/article/view/5437
Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common pre-malignant conditions in western countries with a prevalence of 3.2% in the Caucasian general population 50 years of age or older. […] A recent study based on 77,469 healthy adults enrolled in a nationwide population-based prospective cancer screening trial in the USA identified 71 individuals who developed MM during the course of the study. Using serially-collected pre-diagnostic serum samples obtained up to almost 10 years prior to the diagnosis of MM, all MM cases were found to have been preceded by MGUS. […] This finding establishes a key role for MGUS in the pathway to MM. Indeed, long-term follow-up of MGUS patients reveals an average 1% annual risk of developing lymphoproliferative malignancies.
#10 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK507880/
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] No specific cause of non-IgM MGUS has been identified. However, the disease may be associated with some non-malignant disorders such as connective tissue disorders, peripheral neuropathies, dermatological diseases such as acquired C1 esterase inhibitor deficiency (angioedema), endocrine diseases, and liver infections such as hepatitis C virus infection and HIV liver disease. […] Population-based studies from northern Europe and the United States show increased risk of MGUS among first-degree relatives of those with MGUS or myeloma, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
#11 Monoclonal Gammopathy of Undetermined Significance (MGUS)
https://www.healthline.com/health/how-serious-is-mgus
Monoclonal gammopathy of undetermined significance (MGUS) is an abnormal finding of a blood test. It means theres a specific protein present in your blood and is an early sign of certain types of a cancer called myeloma. […] Doctors and scientists arent sure exactly what causes MGUS. Its thought that certain genetic changes and environmental factors may affect whether a person develops this condition. […] What doctors do know is that MGUS causes abnormal plasma cells in the bone marrow to produce M protein. […] The prevalence of MGUS is twice as high in African Americans when compared with white Americans. This is most likely be due to genetic factors. Environmental factors are possible, but evidence is lacking. […] Studies indicate that people with a first-degree relative with MGUS or multiple myeloma have a 2 to 3 times higher risk of developing MGUS. A first-degree relative is a full sibling or biological parent. […] Studies have also found that a family history of multiple myeloma is associated with a 2 to 4 times increased risk of developing multiple myeloma.
#12 Monoclonal Gammopathies
https://spartanburgregional.staywellsolutionsonline.com/Library/DiseasesConditions/Adult/134,121
Monoclonal gammopathies are conditions in which abnormal proteins (antibodies) are found in the blood. […] The exact cause of MGUS is not known. Infection, immune system problems, and the environment may play a role. But experts have not found a clear link yet. […] Experts do know that the abnormal proteins are not caused by a certain diet or from eating dietary proteins. […] The chance of getting MGUS grows with age, but it’s not common. It occurs more in people older than 50. […] There is no risk for monoclonal gammopathies in first-degree family members. […] MGUS does not usually cause symptoms, so it doesn’t need to be treated. […] Since MGUS may lead to a more serious condition, regular monitoring and checkups are recommended throughout your life. […] MGUS may lead to a more serious condition. So checkups may be recommended throughout your life to find problems as early as possible.
#13 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. The cause of MGUS is unknown, though the same theories that apply to the pathogenesis of MM may be valid in MGUS. […] Risk factors for MGUS have been identified. Nonmodifiable risk factors include the following: Older age, Male sex, Black race, Family history of MGUS and related diseases. […] Other risk factors include the following: Specific prior infections (eg, pneumonia, hepatitis, meningitis, HIV), Inflammatory disorders, Autoimmune disease, Smoking, Pesticide exposure (eg, aldrin, dieldrin, permethrin). […] Most cases of MGUS involve IgG or IgA monoclonal cell populations. […] Several studies have confirmed that characteristic genetic abnormalities of MM are present in patients with MGUS.
#14 What is the significance of monoclonal gammopathy of undetermined significance?
https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/
Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal paraprotein in the blood, without the characteristic end organ damage seen in multiple myeloma. […] Several mechanisms have been suggested to account for the development of MGUS, including cytogenetic and bone marrow microenvironment changes. Chromosomal translocations are common, often involving regions responsible for the heavy-chain component of immunoglobulin. […] The renal complications associated with MGUS are so well recognised that it is referred to as monoclonal gammopathy of renal significance to indicate the causal relationship between the monoclonal gammopathy and renal damage. […] Monoclonal gammopathy of undetermined significance carries a risk of progression to myeloma and is associated with several complications, including renal impairment, infection and fracture, which can have not only significant morbidity but also potential treatments.
#15 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. The cause of MGUS is unknown, though the same theories that apply to the pathogenesis of MM may be valid in MGUS. […] Risk factors for MGUS have been identified. Nonmodifiable risk factors include the following: Older age, Male sex, Black race, Family history of MGUS and related diseases. […] Other risk factors include the following: Specific prior infections (eg, pneumonia, hepatitis, meningitis, HIV), Inflammatory disorders, Autoimmune disease, Smoking, Pesticide exposure (eg, aldrin, dieldrin, permethrin). […] Most cases of MGUS involve IgG or IgA monoclonal cell populations. […] Several studies have confirmed that characteristic genetic abnormalities of MM are present in patients with MGUS.
#16 MGUS | Harold C. Simmons Comprehensive Cancer Center | Condition | UT Southwestern Medical Center
https://utswmed.org/conditions-treatments/mgus/
MGUS occurs when a group of plasma cells or B lymphocytes in the bone marrow undergo cellular changes. The exact causes of this are not well understood, but changes in the genes of plasma cells and lymphocytes might play a role. As with most precursor conditions, the causes of MGUS are an active area of research. […] Several factors may increase the risk of developing MGUS or a related monoclonal gammopathy: […] Age: The condition is more common in older adults, especially those over 70. […] Race: African Americans and people of African descent have a higher risk of developing MGUS compared with other ethnicities. […] Sex: It is more common in men than in women. […] Environmental exposure: Being around certain chemicals, such as pesticides and industrial solvents, may increase someone’s risk. […] Family history: Having close family members with MGUS may raise the likelihood of developing the condition.
#17 Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)
https://www.cancernetwork.com/view/management-monoclonal-gammopathy-undetermined-significance-mgus-and-smoldering-multiple-myeloma-smm
The cause of MGUS is not known. There is a genetic element in some patients. […] Radiation exposure may also be a factor. MGUS developed in 1,082 of 52,525 Nagasaki atomic bomb survivors. […] The risk of MM in agricultural workers has been higher in a number of case control studies. […] In a report of 1,000 black women and 996 white women of similar age, 3.9% of the black women had MGUS, while 2.1% of the white women had MGUS.
#18 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#19 Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)
https://www.cancernetwork.com/view/management-monoclonal-gammopathy-undetermined-significance-mgus-and-smoldering-multiple-myeloma-smm
The cause of MGUS is not known. There is a genetic element in some patients. […] Radiation exposure may also be a factor. MGUS developed in 1,082 of 52,525 Nagasaki atomic bomb survivors. […] The risk of MM in agricultural workers has been higher in a number of case control studies. […] In a report of 1,000 black women and 996 white women of similar age, 3.9% of the black women had MGUS, while 2.1% of the white women had MGUS.
#20 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. The cause of MGUS is unknown, though the same theories that apply to the pathogenesis of MM may be valid in MGUS. […] Risk factors for MGUS have been identified. Nonmodifiable risk factors include the following: Older age, Male sex, Black race, Family history of MGUS and related diseases. […] Other risk factors include the following: Specific prior infections (eg, pneumonia, hepatitis, meningitis, HIV), Inflammatory disorders, Autoimmune disease, Smoking, Pesticide exposure (eg, aldrin, dieldrin, permethrin). […] Most cases of MGUS involve IgG or IgA monoclonal cell populations. […] Several studies have confirmed that characteristic genetic abnormalities of MM are present in patients with MGUS.
#21 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#22 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#23 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
The risk of progression to MM or other lymphoproliferative disorder is present at a constant rate throughout the remainder of a patient’s life. […] Although autoimmune disease is a well-described risk factor for the development of MGUS, a Swedish population-based study determined that patients with a history of autoimmune disease have a significantly lower risk of progression from MGUS to MM or other lymphoproliferative diseases.
#24 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK507880/
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] No specific cause of non-IgM MGUS has been identified. However, the disease may be associated with some non-malignant disorders such as connective tissue disorders, peripheral neuropathies, dermatological diseases such as acquired C1 esterase inhibitor deficiency (angioedema), endocrine diseases, and liver infections such as hepatitis C virus infection and HIV liver disease. […] Population-based studies from northern Europe and the United States show increased risk of MGUS among first-degree relatives of those with MGUS or myeloma, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
#25 MGUS | CFCH | Centre for Clinical Haematology
https://cfch.com.sg/monoclonal-gammopathy-of-undetermined-significance-mgus/
Family history: If a close family member has MGUS, you have a higher risk of developing it. […] Autoimmune disorders: Some autoimmune disorders, including pernicious anaemia and lupus, can increase the risk of MGUS. […] While MGUS itself is a non-cancerous condition, it can sometimes progress leading to the development of more serious diseases, such as Myeloma and Lymphoma. […] It is estimated that about 1 out of 100 patients with MGUS develop cancer each year. […] Many patients will develop myeloma from an underlying predisposing condition known as monoclonal gammopathy of undetermined significance (MGUS).
#26 Risks and causes of myeloma | Cancer research UK
https://www.cancerresearchuk.org/about-cancer/myeloma/risks-causes
Some people with myeloma already have a rare medical condition called MGUS. MGUS stands for monoclonal gammopathy of undetermined significance. […] MGUS means there are too many large protein molecules (immunoglobulins) in the blood. […] In most people MGUS doesn’t cause any symptoms or need treatment. […] MGUS does not usually need treatment. Some people with MGUS go on to develop myeloma, so your specialist or GP will see you regularly for check ups. About 1 out of 100 people with MGUS (1%) develop myeloma each year. […] An autoimmune condition called pernicious anaemia appears to increase the risk of myeloma and MGUS.
#27 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
The risk of progression to MM or other lymphoproliferative disorder is present at a constant rate throughout the remainder of a patient’s life. […] Although autoimmune disease is a well-described risk factor for the development of MGUS, a Swedish population-based study determined that patients with a history of autoimmune disease have a significantly lower risk of progression from MGUS to MM or other lymphoproliferative diseases.
#28
https://haematologica.org/article/view/5437
Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common pre-malignant conditions in western countries with a prevalence of 3.2% in the Caucasian general population 50 years of age or older. […] A recent study based on 77,469 healthy adults enrolled in a nationwide population-based prospective cancer screening trial in the USA identified 71 individuals who developed MM during the course of the study. Using serially-collected pre-diagnostic serum samples obtained up to almost 10 years prior to the diagnosis of MM, all MM cases were found to have been preceded by MGUS. […] This finding establishes a key role for MGUS in the pathway to MM. Indeed, long-term follow-up of MGUS patients reveals an average 1% annual risk of developing lymphoproliferative malignancies.
#29 Monoclonal gammopathy of undetermined significance â Knowledge and References â Taylor & Francis
https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Hematology/Monoclonal_gammopathy_of_undetermined_significance/
Approximately 3% to 5% of individuals older than 50 have a monoclonal gammopathy of undetermined significance (MGUS) in absence of clinical evidence of myeloma. […] Monoclonal gammopathy of undetermined significance (MGUS) is more prevalent with advanced age, occurring in roughly 5% of all individuals 65 and older.
#30 MGUS (Monoclonal Gammopathy Of Unknown Significance) | Macmillan Cancer Support
https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/pre-cancerous-and-genetic-conditions/mgus
MGUS (monoclonal gammopathy of unknown significance) is a non-cancerous condition where the body makes an abnormal protein. […] Doctors do not know what causes MGUS, but different things are known to increase the risk of it developing. […] MGUS is more common in older people. It is rare in people under the age of 40. […] MGUS is more common in black people than in white people. […] MGUS is almost twice as common in men than in women. […] People who have a close family member (such as a parent, brother or sister) with MGUS have a slightly increased risk of developing it. […] Autoimmune diseases cause the body’s immune system to attack healthy cells in the body. Some may slightly increase the risk of developing MGUS. […] MGUS does not usually cause any symptoms. […] Doctors do not know why some people with MGUS develop a cancer and others do not.
#31 MGUS | CFCH | Centre for Clinical Haematology
https://cfch.com.sg/monoclonal-gammopathy-of-undetermined-significance-mgus/
Monoclonal gammopathy of undetermined significance (MGUS) is a disorder caused by the production of an abnormal protein called monoclonal protein in the blood. […] The exact cause of MGUS is not known. Environmental factors and genetic abnormalities appear to trigger the development of this disease. […] MGUS may also occur when the functions of a type of white blood cell, called plasma cells, that formed in the bone marrow are affected. […] The factors that can increase the risk of MGUS include: Age: The incidence of MGUS is higher in older people. People under the age of 40 rarely develop this disorder. […] Gender: MGUS is nearly two times more common in men compared to women. […] Ethnicity: The prevalence of MGUS is higher in Africans, and African Americans compared to that in Europeans.
#32 MGUS – Myeloma UK
https://www.myeloma.org.uk/understanding-myeloma/related-conditions/mgus/
Monoclonal gammopathy of undetermined significance, or âMGUSâ, is a condition related to myeloma but it is not a cancer. […] The exact cause or causes of MGUS are not yet known but is thought to involve complex changes at the genetic level. […] We do know that there are some risk factors that increase the chance of developing MGUS. The risk increases as people get older, itâs more common in men and in people from Black ethnic groups than white or Asian, and more common among people with a close relation with the condition. […] Weâre working to understand what may cause people with MGUS to develop myeloma.
#33 Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)
https://www.cancernetwork.com/view/management-monoclonal-gammopathy-undetermined-significance-mgus-and-smoldering-multiple-myeloma-smm
The cause of MGUS is not known. There is a genetic element in some patients. […] Radiation exposure may also be a factor. MGUS developed in 1,082 of 52,525 Nagasaki atomic bomb survivors. […] The risk of MM in agricultural workers has been higher in a number of case control studies. […] In a report of 1,000 black women and 996 white women of similar age, 3.9% of the black women had MGUS, while 2.1% of the white women had MGUS.
#34 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#35 What is the difference between MGUS and multiple myeloma?
https://www.medicalnewstoday.com/articles/mgus-vs-multiple-myeloma
Monoclonal gammopathy of unknown significance (MGUS) causes people to have abnormal antibodies in their blood. Despite this, they often appear otherwise healthy. […] MGUS is a noncancerous condition affecting plasma cells. It sometimes precedes MM. […] Certain conditions can increase an individual’s risk for MGUS. These include being older, being male, being Black, and having a family history of MGUS. […] Some additional risk factors that may be associated with MGUS include inflammatory disorders, smoking, and several specific past infections. […] Additionally, it is important to note that MGUS has the same risk factors as MM.
#36 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#37 Monoclonal Gammopathies – Stanford Medicine Children’s Health
https://www.stanfordchildrens.org/en/topic/default?id=monoclonal-gammopathies-134-121
The exact cause of MGUS is not known. Infection, immune system problems, and the environment may play a role. But experts have not found a clear link yet. […] Experts do know that the abnormal proteins are not caused by a certain diet or from eating dietary proteins.
#38 Monoclonal Gammopathy of Undetermined Significance (MGUS) â
https://watch.giblib.com/video/10267
We clearly know what are some of the key genomic features that make this abnormal clonal plasma subpopulation different from the normal plasma cells. […] If you were to ask what actually causes that, thatâs where we donât quite know. […] There is an increased risk of developing an MGUS with age. […] The other key factors are race. […] Family history has been a big one, so first-degree relatives of patients with MGUS or myeloma have roughly a 2 to 3 fold higher risk of developing MGUS than other individuals. […] There have been several studies to show that obesity can be defined by a BMI greater than 30 kilograms. […] The biggest one that has the most data on is really oneâs exposures to various pesticides and chemicals. […] Are there various types of MGUS and do some carry a more ominous prognosis than others?
#39 Monoclonal Gammopathy of Undetermined Significance (MGUS) â
https://watch.giblib.com/video/10267
Monoclonal gammopathies represent abnormal proteins produced by plasma cells. The most common monoclonal gammopathy is Monoclonal Gammopathy of Undetermined Significance or MGUS. While MGUS itself is not a malignancy and doesnât require treatment, patients with MGUS have an increased risk of developing a variety of hematologic malignancies and therefore do require surveillance. […] Monoclonal Gammopathy of Undetermined Significance (MGUS) is a plasma cell disorder arising somewhere in the bone marrow. […] Patients with this monoclonal gammopathy of undetermined significance have a lifetime risk of progression to serious disorders such as multiple myeloma, light chain amyloidosis, or other low-grade lymphoproliferative disorders. […] The unique thing about them is that they have abnormally regained the capacity to proliferate.
#40
https://step2.medbullets.com/oncology/422784/monoclonal-gammopathy-of-undetermined-significance-mgus
ETIOLOGY […] Pathophysiology […] not fully clear; however, several oncogenic events affecting the plasma cell leads to clonal expansion […] leads to the overproduction of monoclonal proteins […] […] […] may be due to the development of multiple myeloma or other lymphoproliferative malignancies
#41 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK507880/
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] No specific cause of non-IgM MGUS has been identified. However, the disease may be associated with some non-malignant disorders such as connective tissue disorders, peripheral neuropathies, dermatological diseases such as acquired C1 esterase inhibitor deficiency (angioedema), endocrine diseases, and liver infections such as hepatitis C virus infection and HIV liver disease. […] Population-based studies from northern Europe and the United States show increased risk of MGUS among first-degree relatives of those with MGUS or myeloma, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
#42 What Is MGUS? – Monoclonal Gammopathy of Undetermined Significance | Roswell Park Comprehensive Cancer Center – Buffalo, NY
https://www.roswellpark.org/cancer/multiple-myeloma/about/mgus
MGUS is caused by monoclonal plasma cells. Monoclonal means we think they all began from the same cell. […] When plasma cells become abnormal, they do not stop multiplying, and they produce antibodies that are not targeted to specific germs, so they are useless in fighting infection. […] The antibodies produced by those abnormal cells are called monoclonal proteins (M-proteins), and they can be measured in the blood and urine. […] Some patients with MGUS may also develop renal problems when monoclonal proteins accumulate in the kidney tissue. […] MGUS is not a disease, because most of the time it causes no symptoms, but there is a very low risk that it can progress into a symptom-causing disease.
#43 Myeloma – Leukaemia Foundation
https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/myeloma/mgus/
There is no specific cause for myeloma. It is more common in men than women. The risk of developing myeloma increases with age. Some factors that can increase your risk of developing myeloma include: […] A history of monoclonal gammopathy of undetermined significance (MGUS). […] About 20% of people with MGUS develop myeloma. […] MGUS is a disorder of the plasma cells. […] People with MGUS produce an abnormal protein called an M-protein rather than antibodies. […] The M-protein can build up in your blood stream and urine. […] The M-protein reduces your bodyâs ability to fight infection. […] MGUS doesnât require any treatment, but monitoring is recommended.
#44 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. The cause of MGUS is unknown, though the same theories that apply to the pathogenesis of MM may be valid in MGUS. […] Risk factors for MGUS have been identified. Nonmodifiable risk factors include the following: Older age, Male sex, Black race, Family history of MGUS and related diseases. […] Other risk factors include the following: Specific prior infections (eg, pneumonia, hepatitis, meningitis, HIV), Inflammatory disorders, Autoimmune disease, Smoking, Pesticide exposure (eg, aldrin, dieldrin, permethrin). […] Most cases of MGUS involve IgG or IgA monoclonal cell populations. […] Several studies have confirmed that characteristic genetic abnormalities of MM are present in patients with MGUS.
#45 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK507880/
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] No specific cause of non-IgM MGUS has been identified. However, the disease may be associated with some non-malignant disorders such as connective tissue disorders, peripheral neuropathies, dermatological diseases such as acquired C1 esterase inhibitor deficiency (angioedema), endocrine diseases, and liver infections such as hepatitis C virus infection and HIV liver disease. […] Population-based studies from northern Europe and the United States show increased risk of MGUS among first-degree relatives of those with MGUS or myeloma, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.
#46 What is the significance of monoclonal gammopathy of undetermined significance?
https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/
Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal paraprotein in the blood, without the characteristic end organ damage seen in multiple myeloma. […] Several mechanisms have been suggested to account for the development of MGUS, including cytogenetic and bone marrow microenvironment changes. Chromosomal translocations are common, often involving regions responsible for the heavy-chain component of immunoglobulin. […] The renal complications associated with MGUS are so well recognised that it is referred to as monoclonal gammopathy of renal significance to indicate the causal relationship between the monoclonal gammopathy and renal damage. […] Monoclonal gammopathy of undetermined significance carries a risk of progression to myeloma and is associated with several complications, including renal impairment, infection and fracture, which can have not only significant morbidity but also potential treatments.
#47 IgM Monoclonal Gammopathy of Undetermined Significance – DoveMed
https://www.dovemed.com/diseases-conditions/igm-monoclonal-gammopathy-undetermined-significance
There is evidence to suggest a genetic predisposition to the development of IgM MGUS, as evidenced by familial clustering of the condition in some cases. […] Chronic antigenic stimulation, such as persistent exposure to infectious agents, autoimmune triggers, or environmental factors, may contribute to the development of IgM MGUS. […] Overall, IgM Monoclonal Gammopathy of Undetermined Significance is likely the result of a complex interplay of genetic susceptibility, environmental exposures, and immune dysregulation.
#48 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate
https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance
Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. […] MGUS occurs in over 3 percent of the White population over the age of 50 and is typically detected as an incidental finding when individuals undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders (eg, peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, or elevated erythrocyte sedimentation rate). […] There are three distinct clinical types of MGUS, each with a risk of progressing through a unique intermediate (more advanced) premalignant stage and then to a malignant plasma cell dyscrasia or lymphoproliferative disorder: […] Non-IgM MGUS (IgG, IgA, or IgD MGUS) â Non-IgM MGUS is the most common subtype of MGUS and has the potential to progress to smoldering (asymptomatic) multiple myeloma and to symptomatic multiple myeloma.
#49 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate
https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance
Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. […] MGUS occurs in over 3 percent of the White population over the age of 50 and is typically detected as an incidental finding when individuals undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders (eg, peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, or elevated erythrocyte sedimentation rate). […] There are three distinct clinical types of MGUS, each with a risk of progressing through a unique intermediate (more advanced) premalignant stage and then to a malignant plasma cell dyscrasia or lymphoproliferative disorder: […] Non-IgM MGUS (IgG, IgA, or IgD MGUS) â Non-IgM MGUS is the most common subtype of MGUS and has the potential to progress to smoldering (asymptomatic) multiple myeloma and to symptomatic multiple myeloma.
#50
https://link.springer.com/article/10.1007/s12254-020-00630-z
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant hematological condition arising from Bcells, characterized by the presence of monoclonal immunoglobulin production, also known as paraprotein. It is found in up to 3% of individuals over the age of 50 years. […] Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant Bcell neoplasia usually arising from plasma cells and less frequently from lymphoplasmacytic cells. It is defined as a serum monoclonal protein of less than 30g/L, less than 10% of clonal plasma or lymphoplasmacytic cells in the bone marrow, and the absence of end-organ damage, myeloma defining events, or any constitutional symptoms. […] MGUS has an overall low risk of progression to multiple myeloma (MM) or other associated diseases. Depending on the immunoglobulin subtype, the rate of progression can vary from 0.3% per year in light-chain MGUS to 1.5% in IgM MGUS.
#51 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate
https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance
IgM MGUS â IgM MGUS accounts for approximately 15 percent of MGUS cases. It is considered separately from the non-IgM MGUS because it has the potential to progress to smoldering WaldenstrÃ¶ m macroglobulinemia and to symptomatic WaldenstrÃ¶ m macroglobulinemia, and less often to lymphoma or AL amyloidosis. Infrequently, IgM MGUS can progress to IgM multiple myeloma.
#52 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate
https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance
IgM MGUS â IgM MGUS accounts for approximately 15 percent of MGUS cases. It is considered separately from the non-IgM MGUS because it has the potential to progress to smoldering WaldenstrÃ¶ m macroglobulinemia and to symptomatic WaldenstrÃ¶ m macroglobulinemia, and less often to lymphoma or AL amyloidosis. Infrequently, IgM MGUS can progress to IgM multiple myeloma.
#53
https://link.springer.com/article/10.1007/s12254-020-00630-z
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant hematological condition arising from Bcells, characterized by the presence of monoclonal immunoglobulin production, also known as paraprotein. It is found in up to 3% of individuals over the age of 50 years. […] Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant Bcell neoplasia usually arising from plasma cells and less frequently from lymphoplasmacytic cells. It is defined as a serum monoclonal protein of less than 30g/L, less than 10% of clonal plasma or lymphoplasmacytic cells in the bone marrow, and the absence of end-organ damage, myeloma defining events, or any constitutional symptoms. […] MGUS has an overall low risk of progression to multiple myeloma (MM) or other associated diseases. Depending on the immunoglobulin subtype, the rate of progression can vary from 0.3% per year in light-chain MGUS to 1.5% in IgM MGUS.
#54 Monoclonal Gammopathy of Undetermined Significance (MGUS)
https://www.verywellhealth.com/monoclonal-gammopathy-of-undetermined-significance-4771132
Monoclonal gammopathy of undetermined significance (MGUS) is a medical condition that has no symptoms. […] It causes the production of multiple copies of an abnormal protein in your blood. […] A genetic mutation might cause the abnormal plasma cells to start making lots of M protein, and the cells might begin to invade other parts of the body. […] However, sometimes, MGUS precedes a situation in which larger amounts of M proteins are produced. […] The most common kind of MGUS is the non-IgM type. […] For non-IgM MGUS, the risk of developing a blood malignancy is about 0.5% a year. […] For IgM MGUS, the risk of developing a blood malignancy in a given year is higher, about 1%. […] The risk of developing a future blood malignancy if you have light chain MGUS is smaller, around 0.3%.
#55
https://haematologica.org/article/view/7062
Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. […] IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenstrms macroglobulinemia and other lymphoproliferative disorders. […] Obesity, exposure to pesticides, radiation exposure, and personal history of autoimmune diseases, inflammatory conditions and infections are associated with an increased risk of MGUS. […] The importance of MGUS not only lies in the increased risk of developing a hematologic malignancy, but the small clone may also be responsible for severe organ damage through the production of a toxic M-protein which has autoantibody activity or deposits in tissues.
#56 Monoclonal Gammopathy of Undetermined Significance (MGUS)
https://www.verywellhealth.com/monoclonal-gammopathy-of-undetermined-significance-4771132
Monoclonal gammopathy of undetermined significance (MGUS) is a medical condition that has no symptoms. […] It causes the production of multiple copies of an abnormal protein in your blood. […] A genetic mutation might cause the abnormal plasma cells to start making lots of M protein, and the cells might begin to invade other parts of the body. […] However, sometimes, MGUS precedes a situation in which larger amounts of M proteins are produced. […] The most common kind of MGUS is the non-IgM type. […] For non-IgM MGUS, the risk of developing a blood malignancy is about 0.5% a year. […] For IgM MGUS, the risk of developing a blood malignancy in a given year is higher, about 1%. […] The risk of developing a future blood malignancy if you have light chain MGUS is smaller, around 0.3%.
#57
https://haematologica.org/article/view/7062
There is an average risk of progression to MM or, to a lesser extent, other lymphoproliferative disorders of 1% per year. […] The risk of progression for light-chain MGUS is lower when compared to conventional MGUS. […] Presenting features as well as the dynamics of the plasma cell clone during the first years of follow up are helpful in predicting risk of progression of MGUS to symptomatic disease. […] There are currently no data available on extrinsic factors that promote progression. […] So far no predictive factors for progression have been identified for light-chain MGUS. […] The M-protein seems to play a role in the development of several skin disorders including plane xanthoma and Schnitzler syndrome. […] Various kidney disorders are the result of toxic M-proteins produced by the MGUS clone, including monoclonal immunoglobulin deposition disease (MIDD, which includes light-chain deposition disease (LCDD), heavy-chain deposition disease (HCDD), and light- and heavy-chain deposition disease (LHCDD)). […] Importantly, M-protein-associated kidney diseases have a high recurrence rate after kidney transplantation. […] Monoclonal gammopathy of renal significance (MGRS) has been proposed for these pathological conditions, to discriminate them from asymptomatic MGUS.
#58
https://link.springer.com/article/10.1007/s12254-020-00630-z
Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. Further important risk factors include an IgA isotype, an abnormal light chain ratio, a rise in the Mprotein level over time, a bone marrow plasma cell percentage of more than 5%, a reduction of both uninvolved isotypes, and circulating plasma cells in the blood. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] In patients with impaired renal function, evaluation of any underlying conditions that may be the cause for these changes is paramount.
#59 Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS) | Blood Cancer Journal
https://www.nature.com/articles/s41408-021-00406-6
The risk of progression to plasma cell or lymphoid disorders in young patients was predicted by the size of the serum M protein, a potent risk factor with a 3 fold higher risk of progression per unit increase. […] Our study did not find a statistically significant difference in the risk of progression between patients with immune-related conditions and patients without immune-related conditions, although there was a trend towards higher risk of progression in those without a coexisting immune disorder. […] When occurring in the setting of immune-related disorders, the M protein is smaller, more likely to resolve, and may have a lower risk of progression than in patients in whom MGUS is detected without concurrent immune-related disorder.
#60
https://link.springer.com/article/10.1007/s12254-020-00630-z
Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. Further important risk factors include an IgA isotype, an abnormal light chain ratio, a rise in the Mprotein level over time, a bone marrow plasma cell percentage of more than 5%, a reduction of both uninvolved isotypes, and circulating plasma cells in the blood. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] In patients with impaired renal function, evaluation of any underlying conditions that may be the cause for these changes is paramount.
#61
https://haematologica.org/article/view/5437
Additional data suggest that MGUS patients with an abnormal serum – free light chain ratio, non-IgG MGUS and a high serum M-protein level (1.5 g/dL) have a 58% absolute risk of developing MM at 20 years of follow-up, while, in sharp contrast, MGUS patients with none of these risk factors have only a 5% absolute risk of their disease progressing to MM. […] The explanations of our findings probably include a combination of pathogenic mechanisms related to MGUS as well as factors related to the underlying disease which led to medical work-up and detection of MGUS. […] The observed excess mortality among MGUS patients may, at least to a certain degree, reflect various underlying medical illnesses that contributed to the medical work-up eventually leading to the detection of MGUS. […] The observed cause-of-death patterns varied depending on the age of the patients at the time the diagnosis of MGUS was made, and this may have clinical implications.
#62
https://link.springer.com/article/10.1007/s12254-020-00630-z
Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. Further important risk factors include an IgA isotype, an abnormal light chain ratio, a rise in the Mprotein level over time, a bone marrow plasma cell percentage of more than 5%, a reduction of both uninvolved isotypes, and circulating plasma cells in the blood. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] In patients with impaired renal function, evaluation of any underlying conditions that may be the cause for these changes is paramount.
#63
https://link.springer.com/article/10.1007/s12254-020-00630-z
Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. Further important risk factors include an IgA isotype, an abnormal light chain ratio, a rise in the Mprotein level over time, a bone marrow plasma cell percentage of more than 5%, a reduction of both uninvolved isotypes, and circulating plasma cells in the blood. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] In patients with impaired renal function, evaluation of any underlying conditions that may be the cause for these changes is paramount.
#64
https://link.springer.com/article/10.1007/s12254-020-00630-z
Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. Further important risk factors include an IgA isotype, an abnormal light chain ratio, a rise in the Mprotein level over time, a bone marrow plasma cell percentage of more than 5%, a reduction of both uninvolved isotypes, and circulating plasma cells in the blood. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] In patients with impaired renal function, evaluation of any underlying conditions that may be the cause for these changes is paramount.
#65 Monoclonal Gammopathy of Undetermined Significance (MGUS) | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/multiple-myeloma/other-plasma-cell-diseases/monoclonal-gammopathy-undetermined-significance
Monoclonal gammopathy of undetermined significance (MGUS) is not cancer. Theres a small risk it can become cancer. Out of every 100 people with MGUS, each year, 1 or 2 of them will get cancer from MGUS. […] We do not know what causes MGUS. There may be a link to autoimmune diseases, genetics, or environmental factors. […] MGUS can be precancerous, which means it can become cancer. It can be stable for many years, and then turn into another condition. This change happens with very few people. Most people with MGUS never get a more serious condition. […] MGUS can turn into multiple myeloma. It also can turn into another blood disease, either: Amyloidosis, Waldenstrms macroglobulinemia (VAHL-den-strum MA-kroh-GLAH-byoo-lih-NEE-mee-uh). Waldenstrms is a type of non-Hodgkin lymphoma that grows slowly. Its a rare white blood cell cancer that often starts in bone marrow. Its also called lymphoplasmacytic lymphoma.
#66 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
The risk of progression to MM or other lymphoproliferative disorder is present at a constant rate throughout the remainder of a patient’s life. […] Although autoimmune disease is a well-described risk factor for the development of MGUS, a Swedish population-based study determined that patients with a history of autoimmune disease have a significantly lower risk of progression from MGUS to MM or other lymphoproliferative diseases.
#67
https://haematologica.org/article/view/5437
Additional data suggest that MGUS patients with an abnormal serum – free light chain ratio, non-IgG MGUS and a high serum M-protein level (1.5 g/dL) have a 58% absolute risk of developing MM at 20 years of follow-up, while, in sharp contrast, MGUS patients with none of these risk factors have only a 5% absolute risk of their disease progressing to MM. […] The explanations of our findings probably include a combination of pathogenic mechanisms related to MGUS as well as factors related to the underlying disease which led to medical work-up and detection of MGUS. […] The observed excess mortality among MGUS patients may, at least to a certain degree, reflect various underlying medical illnesses that contributed to the medical work-up eventually leading to the detection of MGUS. […] The observed cause-of-death patterns varied depending on the age of the patients at the time the diagnosis of MGUS was made, and this may have clinical implications.
#68
https://haematologica.org/article/view/5437
Additional data suggest that MGUS patients with an abnormal serum – free light chain ratio, non-IgG MGUS and a high serum M-protein level (1.5 g/dL) have a 58% absolute risk of developing MM at 20 years of follow-up, while, in sharp contrast, MGUS patients with none of these risk factors have only a 5% absolute risk of their disease progressing to MM. […] The explanations of our findings probably include a combination of pathogenic mechanisms related to MGUS as well as factors related to the underlying disease which led to medical work-up and detection of MGUS. […] The observed excess mortality among MGUS patients may, at least to a certain degree, reflect various underlying medical illnesses that contributed to the medical work-up eventually leading to the detection of MGUS. […] The observed cause-of-death patterns varied depending on the age of the patients at the time the diagnosis of MGUS was made, and this may have clinical implications.
#69 Risk of MGUS Progression to Myeloma Can Change – NCI
https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk
A new study suggests that a persons risk of progressing from a benign condition called monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma, a type of blood cancer, can change over time. […] MGUS is a condition caused by abnormal changes in plasma cells, which are part of the immune system. […] There is no treatment to prevent MGUS from progressing into multiple myeloma. […] These recommendations assume that the risk of progression stays constant, Dr. Munshi and his colleagues wrote. […] However, if the risk of MGUS progression changed over time, someone whose disease initially appears to be low risk and opts for no follow-up could develop high-risk MGUS and need more intensive follow-up. […] The findings that low- and intermediate-risk MGUS could convert to high-risk MGUS within a few years, the study authors wrote, supports annual blood testing for all individuals diagnosed with MGUS or light-chain MGUS, as well as yearly assessment of a patients clinical risk status. […] A remaining issue is that there are limitations to using the standard blood markers to assess MGUS progression, the editorialists noted. […] Drs. Landgren and Hofmann are exploring other markers that may be more predictive of progression to myeloma.
#70 Risk of MGUS Progression to Myeloma Can Change – NCI
https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk
A new study suggests that a persons risk of progressing from a benign condition called monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma, a type of blood cancer, can change over time. […] MGUS is a condition caused by abnormal changes in plasma cells, which are part of the immune system. […] There is no treatment to prevent MGUS from progressing into multiple myeloma. […] These recommendations assume that the risk of progression stays constant, Dr. Munshi and his colleagues wrote. […] However, if the risk of MGUS progression changed over time, someone whose disease initially appears to be low risk and opts for no follow-up could develop high-risk MGUS and need more intensive follow-up. […] The findings that low- and intermediate-risk MGUS could convert to high-risk MGUS within a few years, the study authors wrote, supports annual blood testing for all individuals diagnosed with MGUS or light-chain MGUS, as well as yearly assessment of a patients clinical risk status. […] A remaining issue is that there are limitations to using the standard blood markers to assess MGUS progression, the editorialists noted. […] Drs. Landgren and Hofmann are exploring other markers that may be more predictive of progression to myeloma.
#71 Risk of MGUS Progression to Myeloma Can Change – NCI
https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk
A new study suggests that a persons risk of progressing from a benign condition called monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma, a type of blood cancer, can change over time. […] MGUS is a condition caused by abnormal changes in plasma cells, which are part of the immune system. […] There is no treatment to prevent MGUS from progressing into multiple myeloma. […] These recommendations assume that the risk of progression stays constant, Dr. Munshi and his colleagues wrote. […] However, if the risk of MGUS progression changed over time, someone whose disease initially appears to be low risk and opts for no follow-up could develop high-risk MGUS and need more intensive follow-up. […] The findings that low- and intermediate-risk MGUS could convert to high-risk MGUS within a few years, the study authors wrote, supports annual blood testing for all individuals diagnosed with MGUS or light-chain MGUS, as well as yearly assessment of a patients clinical risk status. […] A remaining issue is that there are limitations to using the standard blood markers to assess MGUS progression, the editorialists noted. […] Drs. Landgren and Hofmann are exploring other markers that may be more predictive of progression to myeloma.
#72 What is the significance of monoclonal gammopathy of undetermined significance?
https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/
Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal paraprotein in the blood, without the characteristic end organ damage seen in multiple myeloma. […] Several mechanisms have been suggested to account for the development of MGUS, including cytogenetic and bone marrow microenvironment changes. Chromosomal translocations are common, often involving regions responsible for the heavy-chain component of immunoglobulin. […] The renal complications associated with MGUS are so well recognised that it is referred to as monoclonal gammopathy of renal significance to indicate the causal relationship between the monoclonal gammopathy and renal damage. […] Monoclonal gammopathy of undetermined significance carries a risk of progression to myeloma and is associated with several complications, including renal impairment, infection and fracture, which can have not only significant morbidity but also potential treatments.
#73 Monoclonal gammopathy – Wikipedia
https://en.wikipedia.org/wiki/Monoclonal_gammopathy
Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia. The most common form of the disease is monoclonal gammopathy of undetermined significance. […] Causes of paraproteinemia include the following: […] Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years. […] The most common type of paraproteinemia is monoclonal gammopathy of undetermined significance (MGUS). Another form, monoclonal gammopathy of renal significance (MGRS) results in kidney damage and chronic kidney disease due to the effects of monoclonal immunoglobulins.
#74
https://haematologica.org/article/view/7062
There is an average risk of progression to MM or, to a lesser extent, other lymphoproliferative disorders of 1% per year. […] The risk of progression for light-chain MGUS is lower when compared to conventional MGUS. […] Presenting features as well as the dynamics of the plasma cell clone during the first years of follow up are helpful in predicting risk of progression of MGUS to symptomatic disease. […] There are currently no data available on extrinsic factors that promote progression. […] So far no predictive factors for progression have been identified for light-chain MGUS. […] The M-protein seems to play a role in the development of several skin disorders including plane xanthoma and Schnitzler syndrome. […] Various kidney disorders are the result of toxic M-proteins produced by the MGUS clone, including monoclonal immunoglobulin deposition disease (MIDD, which includes light-chain deposition disease (LCDD), heavy-chain deposition disease (HCDD), and light- and heavy-chain deposition disease (LHCDD)). […] Importantly, M-protein-associated kidney diseases have a high recurrence rate after kidney transplantation. […] Monoclonal gammopathy of renal significance (MGRS) has been proposed for these pathological conditions, to discriminate them from asymptomatic MGUS.
#75
https://haematologica.org/article/view/7062
There is an average risk of progression to MM or, to a lesser extent, other lymphoproliferative disorders of 1% per year. […] The risk of progression for light-chain MGUS is lower when compared to conventional MGUS. […] Presenting features as well as the dynamics of the plasma cell clone during the first years of follow up are helpful in predicting risk of progression of MGUS to symptomatic disease. […] There are currently no data available on extrinsic factors that promote progression. […] So far no predictive factors for progression have been identified for light-chain MGUS. […] The M-protein seems to play a role in the development of several skin disorders including plane xanthoma and Schnitzler syndrome. […] Various kidney disorders are the result of toxic M-proteins produced by the MGUS clone, including monoclonal immunoglobulin deposition disease (MIDD, which includes light-chain deposition disease (LCDD), heavy-chain deposition disease (HCDD), and light- and heavy-chain deposition disease (LHCDD)). […] Importantly, M-protein-associated kidney diseases have a high recurrence rate after kidney transplantation. […] Monoclonal gammopathy of renal significance (MGRS) has been proposed for these pathological conditions, to discriminate them from asymptomatic MGUS.
#76
https://haematologica.org/article/view/7062
There is an average risk of progression to MM or, to a lesser extent, other lymphoproliferative disorders of 1% per year. […] The risk of progression for light-chain MGUS is lower when compared to conventional MGUS. […] Presenting features as well as the dynamics of the plasma cell clone during the first years of follow up are helpful in predicting risk of progression of MGUS to symptomatic disease. […] There are currently no data available on extrinsic factors that promote progression. […] So far no predictive factors for progression have been identified for light-chain MGUS. […] The M-protein seems to play a role in the development of several skin disorders including plane xanthoma and Schnitzler syndrome. […] Various kidney disorders are the result of toxic M-proteins produced by the MGUS clone, including monoclonal immunoglobulin deposition disease (MIDD, which includes light-chain deposition disease (LCDD), heavy-chain deposition disease (HCDD), and light- and heavy-chain deposition disease (LHCDD)). […] Importantly, M-protein-associated kidney diseases have a high recurrence rate after kidney transplantation. […] Monoclonal gammopathy of renal significance (MGRS) has been proposed for these pathological conditions, to discriminate them from asymptomatic MGUS.
#77 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#78 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/204297-overview
Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. The cause of MGUS is unknown, though the same theories that apply to the pathogenesis of MM may be valid in MGUS. […] Risk factors for MGUS have been identified. Nonmodifiable risk factors include the following: Older age, Male sex, Black race, Family history of MGUS and related diseases. […] Other risk factors include the following: Specific prior infections (eg, pneumonia, hepatitis, meningitis, HIV), Inflammatory disorders, Autoimmune disease, Smoking, Pesticide exposure (eg, aldrin, dieldrin, permethrin). […] Most cases of MGUS involve IgG or IgA monoclonal cell populations. […] Several studies have confirmed that characteristic genetic abnormalities of MM are present in patients with MGUS.
#79 MGUS | Harold C. Simmons Comprehensive Cancer Center | Condition | UT Southwestern Medical Center
https://utswmed.org/conditions-treatments/mgus/
MGUS occurs when a group of plasma cells or B lymphocytes in the bone marrow undergo cellular changes. The exact causes of this are not well understood, but changes in the genes of plasma cells and lymphocytes might play a role. As with most precursor conditions, the causes of MGUS are an active area of research. […] Several factors may increase the risk of developing MGUS or a related monoclonal gammopathy: […] Age: The condition is more common in older adults, especially those over 70. […] Race: African Americans and people of African descent have a higher risk of developing MGUS compared with other ethnicities. […] Sex: It is more common in men than in women. […] Environmental exposure: Being around certain chemicals, such as pesticides and industrial solvents, may increase someone’s risk. […] Family history: Having close family members with MGUS may raise the likelihood of developing the condition.
#80 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance
https://www.mdpi.com/2673-6357/4/4/27
While recent advances have improved our understanding of the complex genetic and non-genetic factors that cause MGUS progression to MM, the development of MGUS and potentially modifiable risk factors for MGUS are less understood. […] Chronic exposure of the B-cell receptor to persistent exogenous or endogenous antigens may lead to clonal B cell proliferation, antigen-driven selection of B cell clones, and the subsequent development of MGUS. […] We further identified large cohort studies evaluating modifiable risk factors for MGUS and identified prior infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors such as tobacco use and low fruit consumption, environmental exposures, and ionizing radiation as potential risk factors. […] The data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.
#81 Monoclonal Gammopathy of Undetermined Significance (MGUS)
https://www.healthline.com/health/how-serious-is-mgus
Monoclonal gammopathy of undetermined significance (MGUS) is an abnormal finding of a blood test. It means theres a specific protein present in your blood and is an early sign of certain types of a cancer called myeloma. […] Doctors and scientists arent sure exactly what causes MGUS. Its thought that certain genetic changes and environmental factors may affect whether a person develops this condition. […] What doctors do know is that MGUS causes abnormal plasma cells in the bone marrow to produce M protein. […] The prevalence of MGUS is twice as high in African Americans when compared with white Americans. This is most likely be due to genetic factors. Environmental factors are possible, but evidence is lacking. […] Studies indicate that people with a first-degree relative with MGUS or multiple myeloma have a 2 to 3 times higher risk of developing MGUS. A first-degree relative is a full sibling or biological parent. […] Studies have also found that a family history of multiple myeloma is associated with a 2 to 4 times increased risk of developing multiple myeloma.
#82 Monoclonal Gammopathy of Unknown Significance (MGUS) | UAMS Health
https://uamshealth.com/condition/monoclonal-gammopathy-of-unknown-significance/
Monoclonal Gammopathy of Undetermined Significance (MGUS) is a non-cancerous, or benign, condition characterized by the presence in the blood of an abnormal protein produced by plasma cells. […] The abnormal protein is referred to as an Mprotein or paraprotein. It is monoclonal, which means that it is produced by one family of cells that are all identical copies of each other. […] MGUS is considered a benign condition, since there is only a small risk that it will develop into myeloma or a related blood cancer. […] Research at the Myeloma Center suggests that some patients with MGUS are at increased risk for progression to myeloma. […] Our expert scientists at the Myeloma Center are researching what causes the progression of MGUS to myeloma, the genetics of MGUS and myeloma and whether personalized treatment may prevent the progression. […] MGUS is generally considered benign and has no ill effects on overall health or survival. However, regular check-ups are essential, since myeloma typically develops in 1% to 2% of MGUS patients per year.
#83
https://link.springer.com/article/10.1007/s12254-020-00630-z
MGUS is a common premalignant condition found in over 3% of people over the age of 50 years that can precede the development of MM, WM, NHL, AL amyloidosis, or MGRS. While progression rates are low, careful and thorough work-up time of diagnosis is necessary to adequately distinguish MGUS from paraprotein-associated diseases.