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Comprehensive analysis of gene alterations in acute megakaryoblastic leukemia of Down's syndrome

Leukemia volume 17, pages 2250–2252 (2003)Cite this article

TO THE EDITOR

Down's syndrome (DS) children have the 10- to 20-fold increased risk of developing acute leukemia compared with non-DS children. Acute myeloid leukemia (AML) in DS children shows unique characteristics as to be a predominance of the megakaryoblastic leukemia (AMkL) and a preceding history of the transient myeloproliferative disorder (TMD), whose blasts are morphologically and phenotypically indistinguishable from those of AMkL. TMD is developed in about 10% of DS infants and resolves spontaneously in most cases. However, 20% of TMD cases develop AMkL within 3 years, suggesting that additional genetic alterations might occur during the progression from TMD to AMkL. Recently, somatic mutations of the GATA1 gene were reportedly associated with AMkL of DS children.1 In addition, it was reported that GATA1 mutations were present in the TMD blasts, and that the identical GATA1 mutation was found in sequential samples collected from a patient during TMD and subsequent AMkL.2,3,4,5 These results suggested that GATA1 mutations are an early event in DS leukemogenesis and contribute to both pathogenesis of TMD and AMkL, while the acquisition of additional genetic alterations might be necessary for the progression from TMD to AMkL. To date, a lot of genetic alterations, which are involved in the pathogenesis of leukemia, have been accumulated. Especially, mutations of FLT3, N-RAS, p53 and cKIT genes are frequently found in AML, and likely to be associated with the disease progression. To examine whether these mutations are involved in the progression of TMD to AMkL, we comprehensively analyzed these mutations in AMkL and TMD of DS.

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Acknowledgements

This work was supported by Grants-in-Aid from the Japanese Ministry of Health, Labour and Welfare and the Ministry of Education, Culture, Sports, Science and Technology.

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  1. Y Hirose and K Kudo: These authors equally contributed to this work

Authors and Affiliations

  1. Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya, Japan

    Y Hirose & H Kiyoi

  2. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    K Kudo & S Kojima

  3. Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Y Hayashi

  4. Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    T Naoe

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  1. Y Hirose
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  2. K Kudo
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  6. S Kojima
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Hirose, Y., Kudo, K., Kiyoi, H. et al. Comprehensive analysis of gene alterations in acute megakaryoblastic leukemia of Down's syndrome. Leukemia 17, 2250–2252 (2003). https://doi.org/10.1038/sj.leu.2403121

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