title: Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression: potential biological and therapeutic implications.
abstract: Waldenströms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in which the tumor cell population is markedly heterogeneous, consisting of immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma cells. Due to rarity of disease and scarcity of reliable preclinical models, many facets of WM molecular and phenotypic architecture remain incompletely understood. Currently, there are 3 human WM cell lines that are routinely used in experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically present on WM cells. Intrigued by this observation and in an effort to better define the immunophenotypic makeup of this cell line, we conducted a more comprehensive analysis for the presence or absence of other cell surface antigens that are present on the RPCI-WM1 model, as well as those on the two other WM cell lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4 intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers. Overall, differences in surface antigen expression across the 3 cell lines may reflect the tumor clone population predominant in the index patients, from whom the cell lines were developed. Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit.
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Aneel
authors: A
authors: Paulus
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Kasyapa S
authors: KS
authors: Chitta
authors: Department of Flow and Image Cytometry, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Paul K
authors: PK
authors: Wallace
authors: Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Pooja P
authors: PP
authors: Advani
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Sharoon
authors: S
authors: Akhtar
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Maja
authors: M
authors: Kuranz-Blake
authors: Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Sikander
authors: S
authors: Ailawadhi
authors: Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, United States of America.
authors: Asher A
authors: AA
authors: Chanan-Khan
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen