Journal
LEUKEMIA & LYMPHOMA
Volume 54, Issue 2, Pages 387-396Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2012.713481
Keywords
Waldenstrom macroglobulinemia; cell line; preclinical; model
Categories
Funding
- Waterfall Waldenstrom Macroglobulinemia Research Fund
- Leukemia and Lymphoma Society
- NCI Cancer Center Support Grant [P30 CA016056]
- Roswell Park Alliance Foundation, Rapid Tissue Acquisition Program
- Roswell Park Cancer Institute Shared Resource, Mouse Tumor Model Resource (MTMR)
- international Waldenstrom macroglobulinemia foundation (IWMF)
- [R01 CA121044-01]
- [R01 CA097243]
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Understanding the biology of Waldenstrom macroglobulinemia is hindered by a lack of preclinical models. We report a novel cell line, RPCI-WM1, from a patient treated for WM. The cell line secretes human immunoglobulin M (h-IgM) with kappa-light chain restriction identical to the primary tumor. The cell line has a modal chromosomal number of 46 and harbors chromosomal changes such as deletion of 6q21, monoallelic deletion of 9p21 (CDKN2A), 13q14 (RB1) and 18q21 (BCL-2), with a consistent amplification of 14q32 (immunoglobulin heavy chain; IgH) identical to its founding tumor sample. The clonal relationship is confirmed by identical CDR3 length and single nucleotide polymorphisms as well as a matching IgH sequence of the cell line and founding tumor. Both also harbor a heterozygous, non-synonymous mutation at amino acid 265 in the MYD88 gene (L265P). The cell line expresses most of the cell surface markers present on the parent cells. Overall, RPCI-WM1 represents a valuable model to study Waldenstrom macroglobulinemia.
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