Single-cell RNA sequencing reveals chemokine self-feeding of myeloma cells promotes extramedullary metastasis

FEBS Lett. 2020 Feb;594(3):452-465. doi: 10.1002/1873-3468.13623. Epub 2019 Oct 17.

Abstract

In this study, we aimed to determine the mechanisms underlying the initial extramedullary translocation of myeloma cells from bone marrow into peripheral blood. We found that clonal circulating plasma cells (cPCs) are more frequently detected by flow cytometry in extramedullary plasmacytoma (EMP) patients and worsen their prognosis. It is technically much easier to collect single cPCs using FACS than it is to perform EMP biopsy. Therefore, combining EMP imaging with cPC detection may be a promising strategy for prognostic stratification. Here, using single-cell transcriptome analysis, we found that the chemokine CXCL12, a key molecule involved in CXCR4-dependent cell retention in the bone marrow, is abnormally upregulated in cPCs and might initially enable cPCs to evade bone marrow retention and translocate into the bloodstream.

Keywords: chemokine self-feeding; circulating plasma cells; extramedullary plasmacytoma; multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Marrow / metabolism
  • Chemokines / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Neoplasm Metastasis
  • Phenotype
  • Prognosis
  • Sequence Analysis, RNA*
  • Single-Cell Analysis*

Substances

  • Chemokines