REGULATORY ROLES OF THE LIGAND FOR FLK2 FLT3 TYROSINE KINASE RECEPTORON HUMAN HEMATOPOIESIS/

The biological activities of the ligand for the Flk2/Flt3 receptor tyr osine kinase (FL) on human hematopoietic cells are reviewed. In in vit ro studies, FL shows relatively few effects by itself on the prolifera tion and differentiation of hematopoietic cells, but exhibits a potent costimulatory activity in enhancing the proliferation of progenitor c ells of multiple lineages, FL promotes the growth of clonogenic myeloi d progenitor cells in the presence of other cytokines known to be acti ve on myeloid progenitors, including GM-CSF, interleukin 3 (IL-3), kit ligand (KL), M-CSF and G-CSP. In addition, FL synergizes with IL-7 in inducing the proliferation of pro-B cells, whereas PL has little effe ct on the growth of clonogenic erythroid progenitors, Furthermore, FL induces the in vitro expansion of the high proliferative potential col ony-forming cells (HPP-CFC) and stimulates the proliferation of long-t erm culture-initiating cells (LTC-IC), suggesting an activity on the p roliferation of putative stem cells. Thus, FL plays important roles in regulating the proliferation of hematopoietic progenitor cells and, t herefore, may have therapeutic applications.