Eight novel loci implicate shared genetic etiology in multiple myeloma, AL amyloidosis, and monoclonal gammopathy of unknown significance

Leukemia ◽  
2019 ◽  
Vol 34 (4) ◽  
pp. 1187-1191 ◽  
Author(s):  
Subhayan Chattopadhyay ◽  
Hauke Thomsen ◽  
Niels Weinhold ◽  
Iman Meziane ◽  
Stefanie Huhn ◽  
...  
2013 ◽  
Vol 6 (4) ◽  
pp. 445-446
Author(s):  
Marsela Resuli ◽  
Finn Thomsen Nielsen ◽  
Peter Gimsing ◽  
Claus B. Andersen ◽  
Martin Egfjord

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4755-4755
Author(s):  
Lucie Kovarova ◽  
Ivana Buresova ◽  
Ludek Pour ◽  
Renata Suska ◽  
Zdenek Adam ◽  
...  

Abstract Introduction: Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells (PCs). MM and benign monoclonal gammopathy of unknown significance (MGUS) are routinely distinguished on the basis of paraprotein concentration, level of PCs infiltration and the presence or absence of other clinical features. Flowcytometric detection of PCs according to the expression of CD38 and CD138 has limitation in discrimination between normal and abnormal PCs, but this is possible in multicolor phenotypic analysis. The aim of this study is to compare the numbers of normal and abnormal PCs in MGUS and MM subjects and to find some parameter useful for evaluation PCs distribution. Materials and methods: 51 newly diagnosed untreated MM patients (63,9±10,0 years old) and 31 non-treated MGUS subjects (64,2±13,8 years old) were analysed. Lysed whole bone marrows were analysed by flowcytometric immunophenotyping and PCs were indentified by expression of CD38, CD138, CD45 and also CD56 and CD19. Results: Discrimination between normal CD19+ PCs and abnormal CD56+ PCs was done on CD38+CD138+ population. Ratio of normal PCs count and abnormal PCs counts (normal/abnormal=N/A) was used to describe a distribution of PCs. Subjects with MGUS had 0,97±1,65% (average±SD) of CD38+CD138+ cells (median 0,45; range 0,03–7,47%) with average N/A ratio 2,91±3,94 (median 1,36; range 0,01–18,44). Newly diagnosed MM patients had 4,96±9,94% of CD38+CD138+ cells (median 0,85; range 0,02–41,80%) with average N/A ratio 1,70±3,03 (median 0,13; range 0–11,5). In 9,7% MGUS subjects evaluation of distibution of PCs showed transformation of MGUS into MM. In some newly diagnosed MM patients (31,4%) CD38+CD138+ plasma cells were positive for CD19 although they were aberrant and these PCs were mostly CD45+. In some patients (9,7% of MGUS; 17,6% of MM) PC did express neither CD19 nor CD56 and this fact may complicate further evaluation of PCs. Conclusions: Results confirmed that in MGUS subjects we can find lower numbers of PCs which are mostly CD45+CD19+. A majority of plasma cells in newly diagnosed MM patients are abnormal CD56+ PCs and these plasma cells are usually CD45−. Further follow-up of patients can confirm the N/A ratio as a predictive factor for transformation of MGUS into MM and its value for evidence of relapse or progression to active myeloma.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2061-2061
Author(s):  
Theodore Thomas ◽  
Su-Hsin Chang ◽  
Suhong Luo ◽  
Katiuscia O'Brian ◽  
Graham A Colditz ◽  
...  

Abstract Introduction: Multiple Myeloma (MM) is a hematologic malignancy that is universally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS). Obesity is the only known modifiable risk factor for the development of MM, though it is unclear if this is due to increased MGUS incidence or transition of MGUS to MM. In an effort to better understand how obesity may influence the progression of MGUS to MM, we analyzed patient data from the U.S. Veterans Health Administration (VHA). Methods: The VHA database was used to identify patients diagnosed with MGUS between October 1, 1999 and December 31, 2009 using ICD-9 code 273.1. Data was obtained on patient demographics, myeloma direct treatments, weight, height, and other clinical characteristics. Transition to MM was identified using two occurrences of ICD-9 code 203.0 or use of myeloma directed therapy within six months of a single use of ICD-9 code 203.0. Additionally, two investigators reviewed patient records to confirm the diagnosis and verify the diagnosis date. The World Health Organization (WHO) Body Mass Index (BMI) classification (normal-weight: 18.5≤BMI<25, overweight: 25≤BMI<30, and obese: BMI>30) was utilized to categorize BMI. Weight recorded closest to the MGUS diagnosis date was used for BMI calculations. Multivariate survival analysis (controlling for sex, race, BMI, marital status, estimated household income level, modified Charlson co-morbidity score, and creatinine level) was conducted by parametric accelerated failure time left-censored analysis with Weibull-modeled survival time. Results: There were 9,430 unique MGUS patients identified in the VHA database. Progression to MM was noted in 501 (5.3%) patients overall, with a frequency of 98/2139 (4.6%), 236/3932 (6.0%), and 167/3359 (5.0%) of the normal weight, overweight and obese BMI groups, respectively. Survival analysis revealed a statistically significant difference in progression from MGUS to MM in overweight and obese patients compared to normal-weight patients. After controlling for other variables, multivariate analysis demonstrated that obese (HR: 1.53; 95% CI 1.19-1.98) and overweight (HR: 1.45; 95% CI 1.14-1.84) patients were at increased risk of progression from MGUS to MM. Black patients (HR: 1.78; 95% CI 1.46-2.17) were also at increased risk of progression to MM. Conclusions: Patients with Monoclonal Gammopathy of Unknown Significance who are overweight or obese at the time of MGUS diagnosis are at increased risk of progression to Multiple Myeloma compared to normal weight counterparts. Also the data is suggestive that an obese BMI is associated with a higher risk of progression to MM compared to being overweight. Elevated BMI is a modifiable risk factor for progression of MGUS to MM and weight loss is a potential strategy to decrease the risk of progression. Disclosures Carson: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding.


2018 ◽  
Vol 2 (4) ◽  
pp. 252-255
Author(s):  
Cristopher C Briscoe ◽  
Zachary P Nahmias ◽  
Ilana S Rosman ◽  
Milan J Anadkat

A 60-year-old woman with a 13-year history of monoclonal gammopathy of unknown significance (MGUS) presented with worsening nail dystrophy. Prior workup for systemic amyloidosis had been unrevealing, and no other signs of cutaneous disease were present. Nail biopsy was consistent with amyloid deposition, and the patient subsequently underwent autologous hematopoietic stem cell transplantation for AL amyloidosis. In light of the growing literature regarding nail changes as a presenting sign of systemic amyloidosis and the promising utility of nail biopsy, we suggest a low threshold for biopsy in appropriate patients when nail changes characteristic of amyloidosis are refractory to conventional treatment.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2500-2500 ◽  
Author(s):  
Tilmann Bochtler ◽  
Stefan O. Schonland ◽  
Anna Jauch ◽  
Christiane Heiss ◽  
Axel Benner ◽  
...  

Abstract Introduction: Cytogenetic aberrations (CA) have emerged as important pathogenetic and prognostic factors in plasma cell disorders. However, in AL amyloidosis (AL) only a few reports with small numbers of patients have been published. Methods: Using interphase FISH analysis in CD138+ cells, we evaluated the role of CA in a series of 85 AL patients as compared to 146 patients with a monoclonal gammopathy without treatment requirement in a prospective manner. Our panel included IgH translocations t(11;14), t(4;14), t(14;16) and translocation of 14q32 with an unidentified partner, gains of 1q21, 11q23 and 19q13 as well as deletions of 8p21, 13q14 and 17p13. Using these probes we could detect at least one of these aberrations in 95% of AL and in 88% of the control group. Age, gender and plasma cell content were statistically equally distributed among both groups. Results: The most frequent aberration in AL was t(11;14), which was detected in 45% of AL patients as compared to 26% of the control group (p=0,056). It was strongly associated with the lack of an intact immunoglobulin (p&lt;0,001), thus accounting for the frequent light chain only subtype in AL. Markedly, t(11;14) was more frequently found in combination with gain 11q23 in AL than in the control group (20% versus 6%, p = 0.005). Other frequent aberrations in AL included deletion 13q14 (32%) and gain 1q21 (21%), which were observed in the control group at comparable frequencies (34% and 20%). The overlapping character of the underlying plasma cell disorder in both disease entities was also emphasized by the similarities of branching patterns of the five major CA in cluster analysis applied in 169 patients (figure 1). The relation of clinical parameters and chromosomal aberrations was also evaluated. The analyzed CA had no impact on the organ involvement pattern in AL patients. Conclusions: We observed a high frequency for t(11;14) in AL. Apart from this finding, the cytogenetic patterns known in monoclonal gammopathy of unknown significance and multiple myeloma were widely shared by AL amyloidosis. Figure Figure


Leukemia ◽  
2019 ◽  
Vol 33 (7) ◽  
pp. 1817-1821 ◽  
Author(s):  
Hauke Thomsen ◽  
Subhayan Chattopadhyay ◽  
Niels Weinhold ◽  
Pavel Vodicka ◽  
Ludmila Vodickova ◽  
...  

Blood ◽  
2014 ◽  
Vol 123 (16) ◽  
pp. 2513-2517 ◽  
Author(s):  
Niels Weinhold ◽  
David C. Johnson ◽  
Andrew C. Rawstron ◽  
Asta Försti ◽  
Chi Doughty ◽  
...  

Key Points Inherited genetic variation increases risk to developing multiple myeloma through predisposition to MGUS. Loci identified that increase risk of developing MGUS include 2p23.3, 3p22.1, 3q26.2, 6p21.33, 7p15.3, 17p11.2, and 22q13.1.


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