Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression: Potential biological and therapeutic implications

Aneel Paulus, Kasyapa S. Chitta, Paul K. Wallace, Pooja P. Advani, Sharoon Akhtar, Maja Kuranz-Blake, Sikander Ailawadhi, Asher A Chanan Khan

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 ofWM 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 otherWM 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.

Original languageEnglish (US)
Article numbere0122338
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 8 2015

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Waldenstrom Macroglobulinemia
Immunophenotyping
surface antigens
Surface Antigens
Cells
cell lines
Cell Line
therapeutics
plasma cells
Plasma Cells
B-lymphocytes
Lymphocytes
CD38 Antigens
CD19 Antigens
B-Lymphocytes
Therapeutics
CD20 Antigens
non-Hodgkin lymphoma
antigens
Myeloid Progenitor Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression : Potential biological and therapeutic implications. / Paulus, Aneel; Chitta, Kasyapa S.; Wallace, Paul K.; Advani, Pooja P.; Akhtar, Sharoon; Kuranz-Blake, Maja; Ailawadhi, Sikander; Chanan Khan, Asher A.

In: PLoS One, Vol. 10, No. 4, e0122338, 08.04.2015.

Research output: Contribution to journalArticle

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abstract = "Waldenstr{\"o}ms 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 ofWM 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 otherWM 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.",
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AU - Wallace, Paul K.

AU - Advani, Pooja P.

AU - Akhtar, Sharoon

AU - Kuranz-Blake, Maja

AU - Ailawadhi, Sikander

AU - Chanan Khan, Asher A

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