You are here

Nat Commun DOI:10.1038/s41467-022-30694-w

Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes.

Publication TypeJournal Article
Year of Publication2022
AuthorsBustoros, M, Anand, S, Sklavenitis-Pistofidis, R, Redd, R, Boyle, EM, Zhitomirsky, B, Dunford, AJ, Tai, Y-T, Chavda, SJ, Boehner, C, Neuse, CJannes, Rahmat, M, Dutta, A, Casneuf, T, Verona, R, Kastritis, E, Trippa, L, Stewart, C, Walker, BA, Davies, FE, Dimopoulos, M-A, P Bergsagel, L, Yong, K, Morgan, GJ, Aguet, F, Getz, G, Ghobrial, IM
JournalNat Commun
Volume13
Issue1
Pages3449
Date Published2022 Jun 15
ISSN2041-1723
KeywordsDisease Progression, Humans, Multiple Myeloma, Phenotype, Risk, Risk Factors, Smoldering Multiple Myeloma
Abstract

Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models.

DOI10.1038/s41467-022-30694-w
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35705541?dopt=Abstract

Alternate JournalNat Commun
PubMed ID35705541