Human Myeloid Leukemia Xenotransplant Model Demonstrates Leukemia Blood Vessels from Both Human and Mouse Origin.

Leukemia stem cell activity has been extensively studied and has been approached mainly in terms of self-renewal within the hematopoietic compartment. However, given the recent findings that the adult hematopoietic stem cell can provide hemangioblast activity - giving rise to both blood and blood vessels - we questioned whether leukemia also exhibits hemangioblast activity. To test this hypothesis we established a xenotransplant model whereby K562 human myeloid leukemia cells suspended in Matrigel are injected into sublethally irradiated NOD/scid mice. Leukemia loaded Matrigel plugs reliably grew in size in all (n=6) immunocompromised animals. After four weeks of leukemia growth the Matrigel plugs were excised and blood vessels evaluated. Out of six animals, two animals demonstrated human endothelial cells within the Matrigel plug, confirmed by LAMP-1 staining. Interestingly, six out of six animals demonstrated mouse endothelial cells within the Matrigel. This in vivo model demonstrates that human myeloid leukemia can provide hemangioblast activity. Moreover, it appears that within this Matrigel xenotransplant model, host blood vessels are also recruited. The significance of these results highlights the importance in recognizing the hemangioblast potential of leukemia stem cells. Ultimately, complete eradication of leukemia may depend on targeting leukemia-derived blood vessels in addition to cytotoxic therapy directed at the hematopoietic compartment.