Multiple myeloma immunoglobulin lambda translocations portend poor prognosis.
Antineoplastic Agents
/ therapeutic use
DNA Copy Number Variations
Drug Resistance, Neoplasm
/ genetics
Enhancer Elements, Genetic
Gene Expression Regulation, Neoplastic
Genetic Loci
Genome, Human
Humans
Ikaros Transcription Factor
/ genetics
Immunoglobulin lambda-Chains
/ genetics
Immunologic Factors
/ therapeutic use
Lenalidomide
/ therapeutic use
Multiple Myeloma
/ diagnosis
Myeloma Proteins
/ genetics
Plasma Cells
/ immunology
Prognosis
Protein Binding
Proto-Oncogene Proteins c-myc
/ genetics
Recurrence
Survival Analysis
Thalidomide
/ analogs & derivatives
Translocation, Genetic
Whole Genome Sequencing
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
received:
13
07
2018
accepted:
13
03
2019
entrez:
25
4
2019
pubmed:
25
4
2019
medline:
9
5
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31015454
doi: 10.1038/s41467-019-09555-6
pii: 10.1038/s41467-019-09555-6
pmc: PMC6478743
doi:
Substances chimiques
Antineoplastic Agents
0
IKZF1 protein, human
0
Immunoglobulin lambda-Chains
0
Immunologic Factors
0
MYC protein, human
0
Myeloma Proteins
0
Proto-Oncogene Proteins c-myc
0
myeloma immunoglobulins
0
Ikaros Transcription Factor
148971-36-2
Thalidomide
4Z8R6ORS6L
pomalidomide
D2UX06XLB5
Lenalidomide
F0P408N6V4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1911Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201382
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197603
Pays : United States
Organisme : NCI NIH HHS
ID : L30 CA231673
Pays : United States
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