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Genetic complementation of cytokine signaling identifies central role of kinases in hematopoietic cell proliferation

Oncogene volume 23, pages 1214–1220 (2004)Cite this article

Abstract

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.

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Abbreviations

MPDs:

myeloproliferative disorders

FACS:

fluorescence-activated cell sorter

IL-3:

interleukin-3

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Acknowledgements

We acknowledge the efforts of Phil Waite and the members of the Blood Donor Center at the Massachusetts General Hospital in providing patient samples. This work was supported by grants from the NIH (CA76418 and CA86991). GQD is the Birnbaum Scholar of the Leukemia and Lymphoma Society of America. EYK was supported by NIH training Grants (GM07753-22 and CA09541).

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Authors and Affiliations

  1. Whitehead Institute, Nine Cambridge Center, Cambridge, 02142, MA, USA

    Eugene Y Koh & Tong Chen

  2. Department of Biological Chemistry and Molecular Pharmacology, Division of Pediatric Hematology/Oncology, Harvard Medical School, The Children's Hospital and Dana Farber Cancer Institute, Boston, 02115, MA, USA

    George Q Daley

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  1. Eugene Y Koh
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Correspondence to George Q Daley.

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Koh, E., Chen, T. & Daley, G. Genetic complementation of cytokine signaling identifies central role of kinases in hematopoietic cell proliferation. Oncogene 23, 1214–1220 (2004). https://doi.org/10.1038/sj.onc.1207209

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