Human myeloid and lymphoid malignancies in the non-obese diabetic/severe combined immunodeficiency mouse model: Frequency of apoptotic cells in solidtumors and efficiency and speed of engraftment correlate with vascular endothelial growth factor production

Recent studies have suggested that non-obese diabetic/severe combined immun odeficiency (NOD/SCID) mice transplanted with human hematological malignanc ies show higher levels of engraftment compared with other strains. We used this model to compare xenotransplantability of human leukemia and lymphoma cell lines and to investigate angiogenesis in hematopoietic malignancies. T en of 12 evaluated cell Lines were able to engraft NOD/SCID mice within 120 days. A strong correlation was observed between the amount of vascular end othelial growth factor (VEGF) produced in vitro by cultured cells and the e fficiency of tumor engraftment (r = 0.808; P = 0.001), and an inverse corre lation was found between VEGF production and the time of tumor engraftment (r = -0.792; P = 0.006) and between VEGF production and the frequency of ap optotic/ dead cells in solid tumors (r = -0.892; P = 0.007), Moreover, VEGF production correlated with the frequency of endothelial (CD31+/CD34+) cell s in solid tumors (r = 0.897; P = 0.001). Taken together with in vitro data presented here and indicating that the VEGF antagonist Flt-1/Fc chimera in hibits leukemia and lymphoma cell proliferation, our findings support a rol e for tumor-derived VEGF in leukemia and Lymphoma progression. Furthermore, the present study confirms previous observations indicating that VEGF expr ession may play a crucial role in xenotransplantability of human solid mali gnancies in SCID mice. The NOD/SCID model is promising for future evaluatio ns of antiangiogenic drugs, alone or in combination with established chemo- or immunotherapy regimens.