[HTML][HTML] Multiple myeloma immunoglobulin lambda translocations portend poor prognosis

BG Barwick, P Neri, NJ Bahlis, AK Nooka… - Nature …, 2019 - nature.com
BG Barwick, P Neri, NJ Bahlis, AK Nooka, MV Dhodapkar, DL Jaye, CC Hofmeister
Nature communications, 2019nature.com
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 …
Abstract
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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