Genetic complementation of cytokine signaling identifies central role of kinases in hematopoietic cell proliferation.
Molecular evidence suggests a multistep process in the development of acute leukemia. Since inappropriate activation of cytokine signaling cascades is a recurring theme in human leukemia, we performed expression screens to identify genes that transform cytokine-dependent cells. Using retroviral cDNA libraries derived from peripheral blood mononuclear cells of patients with myeloproliferative disorders, we isolated numerous genes that genetically complement cytokine requirements for proliferation of BaF/3 and TF-1 cells. The majority of recovered genes represent members of the kinase family, including several previously linked to leukemogenesis. Our unbiased screen highlights the central role of kinase activation in hematopoietic cell proliferation and identifies a number of potential leukemic oncoproteins.
Koh
Eugene Y
EY
Whitehead Institute, Nine Cambridge Center, Cambridge, MA 02142, USA.
Chen
Tong
T
Daley
George Q
GQ
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D018076:DNA, Complementary; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D011087:Polycythemia Vera / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012190:Retroviridae; D015398:Signal Transduction / Q000235:genetics*; D013922:Thrombocytosis / Q000235:genetics
D016207:Cytokines; D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases