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Abstract
Understanding the biology of Waldenström 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 κ-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 Waldenström macroglobulinemia.
Acknowledgements
We are very grateful to the patient and her family for graciously donating her tumor tissue. This work is partly supported by the Waterfall Waldenström Macroglobulinemia Research Fund (A.C.-K.), the Leukemia and Lymphoma Society (A.C.-K. is a Leukemia and Lymphoma Society Scholar in Clinical Research), and R01 CA121044-01 and R01 CA097243 (K.L. and N.J.N.). This research was also supported, in part, by a NCI Cancer Center Support Grant to the Roswell Park Cancer Institute (P30 CA016056) (N.J.N.). Additional support was provided in part by the Roswell Park Alliance Foundation, “Rapid Tissue Acquisition Program” and the Roswell Park Cancer Institute Shared Resource, “Mouse Tumor Model Resource (MTMR)” (B.A.F.). This work was also supported by grant support from the international Waldenström macroglobulinemia foundation (IWMF) and the leukemia and lymphoma society (A.C.-K.). We are grateful to Dr. Kiersten Marie Miles for her contribution to this project.
Potential conflict of interest
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