Tetraploidy is associated with poor prognosis at diagnosis in multiple myeloma.
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ABSTRACT:
SUBMITTER: Sidana S
PROVIDER: S-EPMC8019381 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
Tetraploidy is associated with poor prognosis at diagnosis in multiple myeloma.
Sidana Surbhi S Jevremovic Dragan D Ketterling Rhett P RP Tandon Nidhi N Greipp Patricia T PT Baughn Linda B LB Dispenzieri Angela A Gertz Morie A MA Rajkumar Sundararajan Vincent SV Kumar Shaji K SK
American journal of hematology 20190206 5
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Project description:Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years and are deemed high risk. Here we analyze structural variants from 795 newly-diagnosed patients as part of the CoMMpass study. We report translocations involving the immunoglobulin lambda (IgL) locus are present in 10% of patients, and indicative of poor prognosis. This is particularly true for IgL-MYC translocations, which coincide with focal amplifications of enhancers at both loci. Importantly, 78% of IgL-MYC translocations co-occur with hyperdiploid disease, a marker of standard risk, suggesting that IgL-MYC-translocated myeloma is being misclassified. Patients with IgL-translocations fail to benefit from IMiDs, which target IKZF1, a transcription factor that binds the IgL enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL translocation as a driver of poor prognosis which may be due to IMiD resistance.
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