Jens Hillengass, MD, Ph.D., Chief of Myeloma, Professor of Oncology at Roswell Park Comprehensive Cancer Center. In this video, he speaks about Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma.
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Overview:
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Symptomatic multiple myeloma is distinguished by osteolytic lesions (OL). The methods by which malignant plasma cells (PC) cause OL in one place while not causing bone damage in others despite thorough invasion remain unexplained. We present a prospective single-cell RNA sequencing (scRNA-seq) investigation of PC derived from random bone marrow aspirates (BM) and matched imaging-guided OL biopsies. Based on scRNA-seq analysis, we examined 148,630 PC from 24 distinct sites in 10 patients and discovered significant inter- and intra-patient heterogeneity. We discover an additional layer of complexity by integrating analyses of anchored scRNA-seq datasets from the BM and OL, in addition to the limited evidence for regional heterogeneity from whole-exome sequencing. PC from OL differ from PC from BM in terms of gene expression, with overexpression of genes linked with myeloma bone disease such as DKK1, HGF, and TIMP-1, as well as recurring downregulation of JUN/FOS, DUSP1, and HBB. PC analysis from longitudinally collected samples showed transcriptional alterations during induction treatment. Our research adds to our understanding of devastating myeloma bone disease.