The Wayne State University Waldenstrom's Macroglobulinemia preclinical model for Waldenstrom's macroglobulinemia.
The Wayne State University Waldenstrom's Macroglobulinemia xenograft model in mice with severe combined immune deficiency (WSU-WM-SCID) is the only preclinical animal model available for this disease. It is based on a permanent, EBV- IgMlambda cell line (WSU-WM) established from a patient with a 10-year history of Waldenstrom's macroglobulinemia (WM). These cells are CD5(-)CD10(+)CD19(+)CD20(+)CD22(+) and have t(8;14) (q24;32), t(12;17) (q24;q21), 2p-. WSU-WM cells also express DNA topoisomerase II (alpha and beta), and are bcl(2)(+)bcl(XL)(+)bax(-). Although the tumor has aggressive biological behavior with c-myc-IgH rearrangement, it has retained the salient features of WM. The breakpoint on 8q24 is downstream of c-myc exon 3, which is not usual for Burkitt-type breakpoints. WSU-WM cells also express both secretory (s(u)) and membrane (m(u)) IgM mRNA and secrete IgM in culture supernatant. Histiologically, WSU-WM-SCID xenograft tumors have lymphoplasmacytoid morphology. These features indicate biological, but not histological evolution. The WSU-WM-SCID is a model of a more aggressive and resistant WM usually seen toward the late stages of disease. It is, therefore, a particularly useful tool in developing new therapeutic strategies for the more aggressive WM, including targeted therapy, which exploits unique molecular characteristics of tumor cells.
Lymphoma Research Laboratory, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Ayad M
AM
Al-Katib
Edith
E
Mensah-Osman
Amro
A
Aboukameel
Ramzi
R
Mohammad
D000818:Animals; D002460:Cell Line / Q000737:chemistry / Q000276:immunology; D003582:Cytogenetics; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D009368:Neoplasm Transplantation; D010641:Phenotype; D008258:Waldenstrom Macroglobulinemia / Q000473:pathology