Development and characterization of the novel MYD88 mutated, 6q deleted BCWM.2 cell line for Waldenström macroglobulinaemia.

Apr 21, 2025

Experts: Shirong Liu,Xia Liu,Choudhury Fabliha Binte Yusuf,Amanda Kofides,Kara M Soroko,Johany Penailillo,Alexa G Canning,Yang Cao,Guang Yang,Lian Xu,Nicholas Tsakmaklis,Hao Sun,Alberto Guijosa,Maria L Guerrera,Christopher J Patterson,Ruben D Carrasco,Prafulla C Gokhale,Shayna R Sarosiek,Jorge J Castillo,John M Hatcher,Zachary R Hunter,Steven P Treon

Cell lines have enabled a comprehensive understanding of disease biology and the advancement of new therapeutics in Waldenström macroglobulinaemia (WM). Herein, we report the development of BCWM.2, a novel WM cell line derived from an untreated symptomatic WM patient. Immunophenotypic and genomic analyses confirmed its origin from primary bone marrow WM cells. Flow cytometry revealed expression of CD19, CD20, CD23, CD38, CD45RA, CD52, immunoglobulin M (IgM) heavy chain and λ light chain on BCWM.2 cells. Whole genome sequencing demonstrated that, unlike BCWM.1, MWCL-1 and RPCI-WM1, which harbour MYD88 mutations, BCWM.2 carries MYD88. BCWM.2 also exhibited hallmark WM genetic aberrations, including 6q deletion and 6p amplification, along with unique mutations in LYN, AKAP9, HDAC5, RUNX3 and SPI1. BCWM.2 cells exhibited optimal growth when co-cultured with HS-5 stromal cells and developed subcutaneous flank masses in all five NOD-SCID mice, along with measurable serum human IgM levels. BCWM.2 cells also showed remarkable sensitivity to the B-cell lymphoma 2 inhibitor venetoclax and the Janus kinase 2/Interleukin-1 receptor-associated kinase 1 inhibitor pacritinib, underscoring their utility for identification of pharmacologically active agents. BCWM.2 represents a novel myeloid differentiation primary response 88-mutated, 6q-deleted cell line with distinct genomic features for in vivo and in vitro studies for WM.
© 2025 British Society for Haematology and John Wiley & Sons Ltd.

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ABOUT THE EXPERTS

Shirong Liu,Xia Liu,Choudhury Fabliha Binte Yusuf,Amanda Kofides,Kara M Soroko,Johany Penailillo,Alexa G Canning,Yang Cao,Guang Yang,Lian Xu,Nicholas Tsakmaklis,Hao Sun,Alberto Guijosa,Maria L Guerrera,Christopher J Patterson,Ruben D Carrasco,Prafulla C Gokhale,Shayna R Sarosiek,Jorge J Castillo,John M Hatcher,Zachary R Hunter,Steven P Treon

Shirong Liu

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Xia Liu

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Choudhury Fabliha Binte Yusuf

Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Amanda Kofides

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Kara M Soroko

Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Johany Penailillo

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Alexa G Canning

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Yang Cao

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Guang Yang

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Lian Xu

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Nicholas Tsakmaklis

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Hao Sun

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Alberto Guijosa

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Maria L Guerrera

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Christopher J Patterson

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Ruben D Carrasco

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.

Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Prafulla C Gokhale

Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Shayna R Sarosiek

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Jorge J Castillo

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

John M Hatcher

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Zachary R Hunter

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Steven P Treon

Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.