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Novel gain-of-function mutation in the extracellular domain of the PDGFRA gene in infant acute lymphoblastic leukemia with t(4;11)(q21;q23)

Leukemia volume 22, pages 2279–2280 (2008)Cite this article

Platelet-derived growth factor receptors α and β (PDGFRA and PDGFRB) belong to the class III receptor tyrosine kinases, which include c-KIT, colony stimulating factor-1 receptor and FLT3.1 PDGFRA and c-KIT are two related receptor tyrosine kinases showing similar structure, and mutations of these genes are detected in gastrointestinal stromal tumor2, 3 and myeloproliferative disorders.4 Recently, we reported a PDGFRA N870S mutation in a 13-year-old boy having acute myelogenous leukemia (AML)-M1 with t(8;21) and an F808L mutation in a 13-year-old girl having AML-M1 with inv(16).5 In addition to point mutations, the FIP1L1-PDGFRA fusion tyrosine kinase resulting from internal deletion of 4q12 locus was described in a subgroup of patients presenting hypereosinophilic syndrome.6 Here, we investigated whether PDGFRA is also implicated in the pathogenesis of acute lymphoblastic leukemia (ALL), and found a mutation which renders a factor-dependent cell line factor-independent by its aberrant tyrosine phosphorylation.

In conclusion, we reported the frequency of PDGFRA mutations in a large series of Japanese pediatric and infantile ALL patients. This is the first report showing a constitutively active PDGFRA mutation found in an ALL patient that may be associated with leukemic cell growth.

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Acknowledgements

We thank S Sohma and H Soga for technical assistance. We also thank Dr S Hirota for wild-type PDGFRA expression plasmid. This work was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor, and Welfare of Japan, a Grant-in-Aid for Scientific Research on Priority Areas, and Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    M Hiwatari

  2. Department of Microbiology, Mie University Graduate School of Medicine, Tsu, Japan

    R Ono & T Nosaka

  3. Department of Molecular Laboratory Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan

    T Taki

  4. Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    M Hiwatari, R Ono, A Hishiya, T Kitamura & T Nosaka

  5. Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan

    E Ishii

  6. Gunma Children's Medical Center, Gunma, Japan

    Y Hayashi

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  1. M Hiwatari
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  8. T Nosaka
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Correspondence to Y Hayashi or T Nosaka.

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Hiwatari, M., Ono, R., Taki, T. et al. Novel gain-of-function mutation in the extracellular domain of the PDGFRA gene in infant acute lymphoblastic leukemia with t(4;11)(q21;q23). Leukemia 22, 2279–2280 (2008). https://doi.org/10.1038/leu.2008.140

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