Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single-cell transcriptomics.

ABSTRACT: Virtually all patients with multiple myeloma become unresponsive to treatment over time. Relapsed/refractory multiple myeloma (RRMM) is accompanied by the clonal evolution of myeloma cells with heterogeneous genomic aberrations and profound changes of the bone marrow microenvironment (BME). However, the molecular mechanisms that drive drug resistance remain elusive. Here, we analyze the heterogeneous tumor cell population and its complex interaction network with the BME of 20 RRMM patients by single cell RNA-sequencing before/after treatment. Subclones with chromosome 1q-gain express a specific transcriptomic signature and frequently expand during treatment. Furthermore, RRMM cells shape an immune suppressive BME by upregulation of inflammatory cytokines and close interaction with the myel

SUBMITTER: Tirier SM 

PROVIDER: S-EPMC8630108 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature