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JAK2, complemented by a second signal from c‐kit or flt‐3, triggers extensive self‐renewal of primary multipotential hemopoietic cells
Author(s) -
Zhao Shengming,
Zoller Karen,
Masuko Masayoshi,
Rojnuckarin Ponlapat,
Yang Xuexian O.,
Parganas Evan,
Kaushansky Kenneth,
Ihle James N.,
Papayannopoulou Thalia,
Willerford Dennis M.,
Clackson Tim,
Blau C.Anthony
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.9.2159
Subject(s) - biology , haematopoiesis , microbiology and biotechnology , stem cell , progenitor cell , proto oncogene proteins c kit , fms like tyrosine kinase 3 , receptor tyrosine kinase , kinase , signal transduction , phosphatidylinositol , tyrosine kinase , stem cell factor , genetics , mutation , gene
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.