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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2325-2331. Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-09-3287. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3287v1 103/6/2325    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Loh, M. L. Articles by Shannon, K. M. Search for Related Content PubMed PubMed Citation Articles by Loh, M. L. Articles by Shannon, K. M. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis Mignon L. Loh, Shashaank Vattikuti, Suzanne Schubbert, Melissa G. Reynolds, Elaine Carlson, Kenneth H. Lieuw, Jennifer W. Cheng, Connie M. Lee, David Stokoe, Jeannette M. Bonifas, Nicole P. Curtiss, Jason Gotlib, Soheil Meshinchi, Michelle M. Le Beau, Peter D. Emanuel, and Kevin M. Shannon From the Department of Pediatrics, University of California, San Francisco; Comprehensive Cancer Center, University of California, San Francisco; Program in Human Genetics, University of California, San Francisco; Cancer Research Institute, University of California, San Francisco; Division of Hematology, Department of Medicine, Stanford University Medical Center, Stanford, CA; Department of Pediatrics, University of Washington, Seattle; Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL; Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham. The PTPN11 gene encodes SHP-2 (Src homology 2 domain–containing protein tyrosine Phosphatase), a nonreceptor tyrosine protein tyrosine phosphatase (PTPase) that relays signals from activated growth factor receptors to p21Ras (Ras) and other signaling molecules. Mutations in PTPN11 cause Noonan syndrome (NS), a developmental disorder characterized by cardiac and skeletal defects. NS is also associated with a spectrum of hematologic disorders, including juvenile myelomonocytic leukemia (JMML). To test the hypothesis that PTPN11 mutations might contribute to myeloid leukemogenesis, we screened the entire coding region for mutations in 51 JMML specimens and in selected exons from 60 patients with other myeloid malignancies. Missense mutations in PTPN11 were detected in 16 of 49 JMML specimens from patients without NS, but they were less common in other myeloid malignancies. RAS, NF1, and PTPN11 mutations are largely mutually exclusive in JMML, which suggests that mutant SHP-2 proteins deregulate myeloid growth through Ras. However, although Ba/F3 cells engineered to express leukemia-associated SHP-2 proteins cells showed enhanced growth factor–independent survival, biochemical analysis failed to demonstrate hyperactivation of the Ras effectors extracellular-regulated kinase (ERK) or Akt. We conclude that SHP-2 is an important cellular PTPase that is mutated in myeloid malignancies. Further investigation is required to clarify how these mutant proteins interact with Ras and other effectors to deregulate myeloid growth. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mutated SHP and AML in leukemias Gen-Sheng Feng Blood 2004 103: 1982-1983. [Full Text] [PDF] This article has been cited by other articles: G.-M. Zou and A. Maitra Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration Mol. Cancer Ther., July 1, 2008; 7(7): 2012 - 2021. [Abstract] [Full Text] [PDF] S. 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