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Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

Leukemia volume 22, pages 686–707 (2008)Cite this article

Abstract

Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak kinases and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphatase are also frequently mutated or their expression is altered in certain hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival pathways. Aberrant regulation of the survival pathways can contribute to uncontrolled cell growth and lead to leukemia. In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia.

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Acknowledgements

JAM and LSS have been supported in part by a grant from the NIH (R01098195). JB was supported in part by the Deutsche Krebshilfe. AB, PL and AT have been supported in part from grants from Associazione Italiana Ricerca sul Cancro (AIRC). AMM has been supported in part by grants from the CARISBO Foundation and the Progetti Strategici Università di Bologna EF2006.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA

    L S Steelman, S L Abrams, J Whelan, F E Bertrand & J A McCubrey

  2. ImClone Systems, New York, NY, USA

    D E Ludwig

  3. Division of Hematology and Oncology, Department of Medicine, Georg-August University, Göttingen, Germany

    J Bäsecke

  4. Department of Biomedical Sciences, University of Catania, Catania, Italy

    M Libra & F Stivala

  5. Regina Elena Cancer Center, Rome, Italy

    M Milella

  6. Department of Cellular Biotechnology and Hematology, University La Sapienza of Rome, Rome, Italy

    A Tafuri

  7. Department of Clinical Sciences, University of Parma, Parma, Italy

    P Lunghi & A Bonati

  8. Unit of Hematology and Bone-Marrow Transplantation, University Hospital of Parma, Parma, Italy

    A Bonati

  9. Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy

    A M Martelli

  10. IGM-CNR, c/o IOR, Bologna, Italy

    A M Martelli

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  1. L S Steelman
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Steelman, L., Abrams, S., Whelan, J. et al. Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia. Leukemia 22, 686–707 (2008). https://doi.org/10.1038/leu.2008.26

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  • DOI: https://doi.org/10.1038/leu.2008.26

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