Phenotypic and functional characterization of a bortezomib-resistant multiple myeloma cell line by flow and mass cytometry

Abstract

Multiple myeloma (MM) is an incurable malignant plasma cell neoplasm. Proteasome inhibitors including Bortezomib (Bz) are used to treat MM, and treatment failure due to drug resistance occurs. Bz-sensitive and -resistant MM cells have distinct immunophenotypic signatures that correlate with clinical outcome. These changes can be identified by fluorescence-based cytometry (FBC), however, FBC is rarely used in predicting Bz resistance. Mass cytometry (MC) is a recently developed variation of flow cytometry that detects heavy metal-ion tagged antibodies using time-of-flight mass spectrometry allowing for detection of up to 38 epitopes simultaneously in a single cell, without significant overlap, exceeding the dimensionality of FBC 3–4-fold. Here, we compared FBC and MC in the immunophenotypic characterization of Bz-sensitive and -resistant human MM cell line U266. We show that Bz-resistant cells are associated with the loss of CD56 and CD66a adhesion molecules as well as an activation signature.

Keywords:

• Multiple myeloma
• cytometry
• bortezomib
• drug resistance

Acknowledgements

Research reported in this publication was funded in part by the University of Minnesota’s Institute of Human Genetics Seed Grant and in part by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. This work was also supported by NIH/NCATS UL1RR033183 & KL2 RR0333182 (ZS) and funds from the Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota (ZS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would like to thank and acknowledge the Mass Cytometry Shared Resource at the University of Minnesota which is supported by the Office of the Vice President for Research (U of MN).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1266621.