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  • Title: JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive self-renewal of primary multipotential hemopoietic cells.
    Author: Zhao S, Zoller K, Masuko M, Rojnuckarin P, Yang XO, Parganas E, Kaushansky K, Ihle JN, Papayannopoulou T, Willerford DM, Clackson T, Blau CA.
    Journal: EMBO J; 2002 May 01; 21(9):2159-67. PubMed ID: 11980713.
    Abstract:
    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.
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