1. A Novel Nonobese Diabetic/Severe Combined Immunodeficient Xenograft Model for Chronic Lymphocytic Leukemia Reflects Important Clinical Characteristics of the Disease
- Author
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Peter R. Ebeling, Thomas Moritz, Joachim R. Göthert, Florian Grabellus, Ludger Sellmann, Philipp Schütt, Michael Flasshove, Siegfried Seeber, Jan Dürig, Ursula R. Sorg, Ulrich Dührsen, and Michael Möllmann
- Subjects
Adult ,Male ,Cancer Research ,T-Lymphocytes ,Lymphocyte ,Chronic lymphocytic leukemia ,Transplantation, Heterologous ,Medizin ,Cell Growth Processes ,Mice, SCID ,Nod ,Peripheral blood mononuclear cell ,Mice ,Mice, Inbred NOD ,Risk Factors ,medicine ,Animals ,Humans ,Doubling time ,Aged ,Aged, 80 and over ,business.industry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Transplantation ,Disease Models, Animal ,Leukemia ,medicine.anatomical_structure ,Oncology ,Immunology ,Female ,Bone marrow ,business ,Neoplasm Transplantation ,Spleen - 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
- Published
- 2007
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