The cellular components of the hematopoietic stem cell (HSC) niche have been gradually identified. However, the niche for malignant hematopoiesis remains to be elucidated. Here, using human leukemia cells which could be transplanted to immunodeficient mice, we studied the in vivo homing, proliferating and surviving sites by immunohistopathology, compared with the corresponding sites for cord blood CD34+ (CBCD34+) cells. The human leukemia cells initially localized on the surface of osteoblasts in the epiphysial region, and expanded to the inner vascular and diaphysial regions within 4 weeks. The percentage of CD34+ leukemia cells in the BM was transiently increased up to 50% and associated with the entry to S phase of the cell-cycle. In vivo BrdU-labeling showed that the epiphysis was the most active site for leukemia cell proliferation. CBCD34+ cells show the similar pattern of homing and proliferation to leukemia samples. After high-dose administration of Ara-C, residual leukemia cells were localized in the perivascular endothelium as well as in contact with the trabecular endosteum. These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche, and that disruption of this niche can potentially facilitate the anti-leukemia effects of various therapies.
Disclosure: No relevant conflicts of interest to declare.