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Influence of IDH on FLT3-ITD status in newly diagnosed AML

Leukemia volume 31, pages 2526–2529 (2017)Cite this article

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Internal tandem duplication (ITD) mutations of the FMS-like Tyrosine Kinase (FLT3) gene are among the most frequently encountered mutations in adult acute myeloid leukemia (AML), occurring in 21-34% of de novo AML, with a higher frequency in younger patients and those with diploid cytogenetics.1, 2, 3, 4 FLT3-ITD mutations confer higher risk disease, particularly in younger patients, where FLT3-ITD is associated with shorter remission durations and high relapse rates after conventional induction therapy.5 Importantly however, the prognostic impact of FLT3-ITD is influenced by, and must be interpreted in the context of, concurrent mutations in other recurrently identified genes, including NPM1 and DNMT3A.5, 6, 7 Isocitrate dehydrogenase (IDH) mutations represent another class of frequently occurring molecular aberrations in AML, with IDH1 and IDH2 mutations noted in 6–16% and 8–19% of AML cases, respectively.8, 9 The prognostic relevance of IDH mutations remains a matter of debate, and appears to differ by the specific IDH mutation and by co-occurring mutations in other myeloid-associated genes.6, 10

IDH1 and IDH2 mutations are noted to co-occur with FLT3-ITD mutations in 15–27% and 8–30% of AML, respectively.9, 11, 12 The prognostic influence of FLT3-ITD+ IDH+ mutation status on outcomes in newly diagnosed AML patients, receiving currently applied FLT3 and non-FLT3 targeted regimens is unclear. The aim of this report is to define the outcome of FLT3-ITD+IDH+ ‘double mutated’ AML patients, in comparison to mutant FLT3-ITD, IDH wild-type-AML patients. Results from our study have important clinical relevance, providing a historical expectation for patients within this AML subset.

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Acknowledgements

CDD, PB involved in designing study, collecting, writing and reviewing manuscript. SP in providing data for the study and reviewing manuscript. KT, NP, ND, CBB, MK, FR, JC and HK involved in providing patients for the study, providing intellectual content, writing and reviewing the manuscript. Our funding was from the following sources – Supported in part by the MD Anderson Cancer Center Support Grant CA016672 and Award Number P01 CA049639.

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Authors and Affiliations

  1. Department of Leukemia, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

    P Boddu, K Takahashi, N Pemmaraju, N Daver, C B Benton, S Pierce, M Konopleva, F Ravandi, J Cortes, H Kantarjian & C D DiNardo

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  1. P Boddu
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  2. K Takahashi
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  3. N Pemmaraju
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  7. M Konopleva
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Correspondence to C D DiNardo.

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Boddu, P., Takahashi, K., Pemmaraju, N. et al. Influence of IDH on FLT3-ITD status in newly diagnosed AML. Leukemia 31, 2526–2529 (2017). https://doi.org/10.1038/leu.2017.244

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