JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive self-renewal of primary multipotential hemopoietic cells

Defining signals that can support the self‐renewal of multipotential hemopoietic progenitor cells (MHPCs) is pertinent to understanding leukemogenesis and may be relevant to developing stem cell‐based therapies. Here we define a set of signals, JAK2 plus either c‐kit or flt‐3, which together can support extensive MHPC self‐renewal. Phenotypically and functionally distinct populations of MHPCs were obtained, depending on which receptor tyrosine kinase, c‐kit or flt‐3, was activated. Self‐renewal was abrogated in the absence of STAT5a/b, and in the presence of inhibitors targeting either the mitogen‐activated protein kinase or phosphatidylinositol 3′ kinase pathways. These findings suggest that a simple two‐component signal can drive MHPC self‐renewal.