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Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD

Leukemia volume 22, pages 1075–1078 (2008)Cite this article

Acute myeloid leukemia (AML) is a relentless hematological malignancy characterized by overproduction of hematopoietic precursor cells with impaired differentiation. Increasing evidences suggest that the development of AML is a multistep process that requires collaboration of at least two classes of mutations: class I mutations activate signal-transduction pathway and confer a proliferation advantage to hematopoietic cells, and the class II mutations affect transcription factors and serve primarily to impair hematopoietic differentiation.1, 2

The PTPN11 gene encodes human SHP2, a nonreceptor tyrosine phosphatase on chromosome 12q24, which participates in signal events downstream of the receptors of growth factors and cytokines and plays a key role in the proliferation and survival of hematopoietic cells. Germ line PTPN11 mutations in patients afflicted with Noonan syndrome were first reported by Tartaglia et al.3 Subsequently, somatic PTPN11 mutations were also found in patients with juvenile myelomonocytic leukemia, myelodysplastic syndrome, childhood AML and acute lymphoblastic leukemia. To the best of our knowledge, however, the characteristics of adult AML with PTPN11 mutation have not been comprehensively studied yet, and the gene alteration that is cooperative with the PTPN11 mutation in the pathogenesis of AML remains largely unknown. In this study, we investigated prevalence and clinical relevance of PTPN11 mutations and their association with other genetic changes from 272 consecutive patients with primary AML. PTPN11 mutations were detected by PCR and direct sequencing using the primers covering exons 3 and 13.4 Mutational analyses of N-RAS, K-RAS, NPM1, FLT3/ITD, FLT3/TKD, CEBPA, KIT, AML1 and MLL/PTD were performed as previously described.5, 6

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Acknowledgements

This work was sponsored partially by grants from the National Science Council of Taiwan, NSC 95-2314-B-002-243-MY2 and the Department of Medical Research at the National Taiwan University Hospital, Taiwan.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, College of Medicine, National Taiwan University, Douliou, Taiwan

    H-A Hou

  2. Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    H-A Hou, C-Y Chen, J-L Tang, M-H Tseng, C-F Huang, R-J Chiou & H-F Tien

  3. Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    W-C Chou, F-Y Lee & M-C Liu

  4. Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan

    L-I Lin

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Hou, HA., Chou, WC., Lin, LI. et al. Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. Leukemia 22, 1075–1078 (2008). https://doi.org/10.1038/sj.leu.2405005

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