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

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^L265P mutations, BCWM.2 carries MYD88^S243N. 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.