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Multiple myeloma immunoglobulin lambda translocations portend poor prognosis
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Journal Article
Multiple myeloma immunoglobulin lambda translocations portend poor prognosis
2019
Overview
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.
Multiple myeloma is frequently characterised by translocation of genes next to the immunoglobulin heavy chain locus. In this study, the authors sequence a large cohort of high risk myeloma samples and find translocations of cMyc to the immunoglobulin heavy chain locus and this is associated with poor prognosis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/15
/ 45/23
/ 45/91
/ Antineoplastic Agents - therapeutic use
/ Chains
/ Drug Resistance, Neoplasm - genetics
/ Drug Resistance, Neoplasm - immunology
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Ikaros Transcription Factor - genetics
/ Ikaros Transcription Factor - immunology
/ Immunoglobulin lambda-Chains - genetics
/ Immunologic Factors - therapeutic use
/ Lenalidomide - therapeutic use
/ Loci
/ Multiple Myeloma - diagnosis
/ Multiple Myeloma - drug therapy
/ Multiple Myeloma - mortality
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - immunology
/ Science
/ Thalidomide - analogs & derivatives
