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Dynamic acquisition of FLT3 or RAS alterations drive a subset of patients with lower risk MDS to secondary AML

Leukemia volume 27, pages 2081–2083 (2013)Cite this article

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The development of massively parallel sequencing technology has allowed the identification of an increasing number of recurrent somatic mutations in myelodysplasitc syndromes (MDS).1 Although identification of these mutations has improved our understanding of the pathogenesis of MDS, a snapshot of molecular alterations at single time point (often at time of diagnosis) does not fully represent the dynamic nature of MDS. Recent whole-genome sequencing of sequential bone marrow samples in small numbers of MDS patients has indicated that mutations could follow a dynamic pattern.2 Therefore, it is becoming apparent that genetic abnormalities of MDS should be analyzed in a time-dependent manner.

FLT3 molecular alterations (FLT3m), including internal tandem duplication (ITD) and tyrosine kinase domain mutation (TKD), and RAS mutations (RASm) are both classified as class 1 mutations in leukemia.3 FLT3m or RASm are identified in approximately 15–30% of acute myeloid leukemia (AML) patients in mutually exclusive manner.4 In contrast to AML, FLT3m and RASm are less frequent in MDS with reported incidence of 0.6–6% and 3–6%, respectively.1, 5 The presence of these mutations has not been associated with difference in prognosis.1, 6, 7 Previous studies, however, focused on the incidence and prognostic impact of FLT3m or RASm at initial diagnosis and only a few studies have evaluated dynamic or temporal acquisition of FLT3m or RASm in MDS.8, 9, 10 In this context, we sought to study the incidence of dynamic acquisition of FLT3m and RASm in lower risk MDS (LR-MDS) and its impact on transformation and survival.

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Acknowledgements

This work was supported by the Ruth and Ken Arnold Fund, the Edward P Evans foundation (GGM and YW), the Celgene Future Leaders in Hematology Award, and Kimberly Patterson Leukemia Research Fellowship (KT). The authors would like to thank Professor Akifumi Takaori at Kyoto University for providing critical review and advice about the project.

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Authors and Affiliations

  1. Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    K Takahashi

  2. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    K Takahashi

  3. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    E Jabbour, S Pierce, H Yang, Y Wei, N Daver, S Faderl, F Ravandi, Z Estrov, J Cortes, H Kantarjian & G Garcia-Manero

  4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    X Wang

  5. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    R Luthra, C Bueso-Ramos & K Patel

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  1. K Takahashi
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Correspondence to G Garcia-Manero.

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Takahashi, K., Jabbour, E., Wang, X. et al. Dynamic acquisition of FLT3 or RAS alterations drive a subset of patients with lower risk MDS to secondary AML. Leukemia 27, 2081–2083 (2013). https://doi.org/10.1038/leu.2013.165

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