A high-throughput electron tomography workflow reveals over-elongated centrioles in relapsed/refractory multiple myeloma

Cell Rep Methods. 2022 Nov 1;2(11):100322. doi: 10.1016/j.crmeth.2022.100322. eCollection 2022 Nov 21.

Abstract

Electron microscopy is the gold standard to characterize centrosomal ultrastructure. However, production of significant morphometrical data is highly limited by acquisition time. We therefore developed a generalizable, semi-automated high-throughput electron tomography strategy to study centrosome aberrations in sparse patient-derived cancer cells at nanoscale. As proof of principle, we present electron tomography data on 455 centrioles of CD138pos plasma cells from one patient with relapsed/refractory multiple myeloma and CD138neg bone marrow mononuclear cells from three healthy donors as a control. Plasma cells from the myeloma patient displayed 122 over-elongated centrioles (48.8%). Particularly mother centrioles also harbored gross structural abnormalities, including fragmentation and disturbed microtubule cylinder formation, while control centrioles were phenotypically unremarkable. These data demonstrate the feasibility of our scalable high-throughput electron tomography strategy to study structural centrosome aberrations in primary tumor cells. Moreover, our electron tomography workflow and data provide a resource for the characterization of cell organelles beyond centrosomes.

Keywords: bone marrow; centriole fragmentation; centriole over-elongation; centrosome; electron tomography; high-throughput electron microscopy; multiple myeloma; plasma cell disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Centrioles* / pathology
  • Centrosome / ultrastructure
  • Electron Microscope Tomography
  • Humans
  • Multiple Myeloma* / diagnostic imaging
  • Workflow