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.
Al-Katib
Ayad M
AM
Lymphoma Research Laboratory, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Mensah-Osman
Edith
E
Aboukameel
Amro
A
Mohammad
Ramzi
R
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