title: A novel nonobese diabetic/severe combined immunodeficient xenograft model for chronic lymphocytic leukemia reflects important clinical characteristics of the disease.
abstract: We here describe a novel xenograft model of chronic lymphocytic leukemia (CLL) generated by infusion of human primary CLL cells into immunodeficient nonobese/severe combined immunodeficient (NOD/SCID) mice. Combined i.v. and i.p. injection of peripheral blood mononuclear cells (PBMC) from 39 patients with CLL resulted in highly reproducible splenic (37 of 39) and peritoneal (35 of 39) engraftment, which remained stable over a time span of 4 to 8 weeks. By comparison, recovery of leukemic cells from bone marrow (21 of 39) or peripheral blood (8 of 22) was substantially lower. The engraftment pattern of CLL PBMC 4 weeks posttransplant was correlated with clinical disease activity: infusion of PBMC from donors with Binet stage A, lymphocyte doubling time of >12 months, and normal lactate dehydrogenase (LDH) serum levels led to marked engraftment of T cells whereas comparably few tumor cells could be detected. In contrast, NOD/SCID mice receiving PBMC from donors with advanced stage Binet C, lymphocyte doubling time of <12 months, and elevated LDH serum levels exhibited predominant engraftment of tumor cells and comparably low numbers of T cells. These results suggest that this model reflects the heterogeneity and important clinical characteristics of the disease, and thus may serve as a tool for preclinical drug testing and investigation of the pathophysiology of CLL.
authors: Department of Hematology, University of Duisburg-Essen Medical School, Essen, Germany.
authors: Jan
authors: J
authors: Dürig
authors: Peter
authors: P
authors: Ebeling
authors: Florian
authors: F
authors: Grabellus
authors: Ursula R
authors: UR
authors: Sorg
authors: Michael
authors: M
authors: Möllmann
authors: Philipp
authors: P
authors: Schütt
authors: Joachim
authors: J
authors: Göthert
authors: Ludger
authors: L
authors: Sellmann
authors: Siegfried
authors: S
authors: Seeber
authors: Michael
authors: M
authors: Flasshove
authors: Ulrich
authors: U
authors: Dührsen
authors: Thomas
authors: T
authors: Moritz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D015203:Reproducibility of Results; D012307:Risk Factors; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D014183:Transplantation, Heterologous