title: 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.
authors.affiliation: a Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics , Mayo Clinic , Rochester , MN , USA.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Baughn
authors.affiliation: b Division of Hematology, Oncology, and Transplantation, Department of Medicine , Minneapolis , MN , USA.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Sachs
authors.affiliation: b Division of Hematology, Oncology, and Transplantation, Department of Medicine , Minneapolis , MN , USA.
authors.forename: Klara E
authors.initials: KE
authors.lastname: Noble-Orcutt
authors.affiliation: c Genetics Cell Biology and Development, Division of Hematopathology, Department of Laboratory Medicine and Pathology , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Mitra
authors.affiliation: c Genetics Cell Biology and Development, Division of Hematopathology, Department of Laboratory Medicine and Pathology , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Van Ness
authors.affiliation: d Division of Hematopathology, Department of Laboratory Medicine and Pathology , University of Minnesota , Minneapolis , MN , USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Linden
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D000069286:Bortezomib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D010641:Phenotype
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D000069286:Bortezomib
keywords: Multiple myeloma; bortezomib; cytometry; drug resistance