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IDH1 and IDH2 mutations in myelodysplastic syndromes and role in disease progression

Leukemia volume 30, pages 980–984 (2016)Cite this article

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Recurrent pathogenic mutations in IDH1 and IDH2 at the conserved amino acid sites IDH1-R132, IDH2-R140 and IDH2-R172 occur in ~20% of patients with acute myeloid leukemia (AML).1 A recent analysis of AML patients at our institution identified IDH1/2 mutations in 20% (n=167) of 826 AML patients, with IDH1/2 mutations occurring most frequently in the setting of diploid karyotype or other intermediate-risk cytogenetics, particularly trisomy 8 (77 vs 53%, P<0.0005). AML patients with IDH1/2 mutations were overall less likely to have a diagnosis of therapy-related AML (8 vs 17%, P=0.003).2

Compared with their frequency in AML, IDH1/2 mutations are less common in myelodysplastic syndromes (MDS), occurring in ~5% of MDS patients, although an incidence as high as 12% has been reported.3, 4, 5, 6, 7, 8 Although IDH1/2 mutations are thought to represent early ‘driver’ events in leukemogenesis with mutational stability over time, reports of IDH1/2 acquisition at the time of leukemic transformation in patients with myeloproliferative neoplasms and MDS have been described.3, 9, 10

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References

  1. Im AP, Sehgal AR, Carroll MP, Smith BD, Tefferi A, Johnson DE et al. DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia 2014; 28: 1774–1783.

    Article  CAS  Google Scholar 

  2. DiNardo CD, Ravandi F, Agresta S, Konopleva M, Takahashi K, Kadia T et al. Characteristics, clinical outcome and prognostic significance of IDH mutations in AML. Am J Hematol 2015; 90: 732–736.

    Article  CAS  Google Scholar 

  3. Pardanani A, Patnaik MM, Lasho TL, Mai M, Knudson RA, Finke C et al. Recurrent IDH mutations in high-risk myelodysplastic syndrome or acute myeloid leukemia with isolated del(5q). Leukemia 2010; 24: 1370–1372.

    Article  CAS  Google Scholar 

  4. Kosmider O, Gelsi-Boyer V, Slama L, Dreyfus F, Beyne-Rauzy O, Quesnel B et al. Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms. Leukemia 2010; 24: 1094–1096.

    Article  CAS  Google Scholar 

  5. Thol F, Weissinger EM, Krauter J, Wagner K, Damm F, Wichmann M et al. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica 2010; 95: 1668–1674.

    Article  CAS  Google Scholar 

  6. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M et al. Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC Cancer 2010; 10: 401.

    Article  Google Scholar 

  7. Lin CC, Hou HA, Chou WC, Kuo YY, Liu CY, Chen CY et al. IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution. Am J Hematol 2014; 89: 137–144.

    Article  CAS  Google Scholar 

  8. Patnaik MM, Hanson CA, Hodnefield JM, Lasho TL, Finke CM, Knudson RA et al. Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: a Mayo Clinic study of 277 patients. Leukemia 2012; 26: 101–105.

    Article  CAS  Google Scholar 

  9. Green A, Beer P . Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 2010; 362: 369–370.

    Article  CAS  Google Scholar 

  10. Molenaar RJ, Thota S, Nagata Y, Patel B, Clemente M, Hirsh C et al. Clinical and biological implications of ancestral and non-ancestral IDH1 and IDH2 mutations in myeloid neoplasms. Leukemia; 2015; 29: 2134–2142.

    Article  CAS  Google Scholar 

  11. Patel KP, Ravandi F, Ma D, Paladugu A, Barkoh BA, Medeiros LJ et al. Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features. Am J Clin Pathol 2011; 135: 35–45.

    Article  CAS  Google Scholar 

  12. Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013; 122: 3616–3627, quiz 99.

    Article  CAS  Google Scholar 

  13. Meggendorfer M, Roller A, Haferlach T, Eder C, Dicker F, Grossmann V et al. SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). Blood 2012; 120: 3080–3088.

    Article  CAS  Google Scholar 

  14. Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014; 28: 241–247.

    Article  CAS  Google Scholar 

  15. Takahashi K, Jabbour E, Wang X, Luthra R, Bueso-Ramos C, Patel K et al. Dynamic acquisition of FLT3 or RAS alterations drive a subset of patients with lower risk MDS to secondary AML. Leukemia 2013; 27: 2081–2083.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by the MD Anderson Cancer Center Support Grant (CCSG) CA016672 and by the generous philanthropic contributions to MD Anderson’s MDS/AML Moon Shot Program. CDD is also supported by the Jeanne F. Shelby Scholarship Fund which has supported her R. Lee Clark Fellow award. This manuscript represents original research which has not been previously published and has not been submitted for publication elsewhere.

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Authors and Affiliations

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

    C D DiNardo, E Jabbour, F Ravandi, K Takahashi, N Daver, M Brandt, S Pierce, H Kantarjian & G Garcia-Manero

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

    M Routbort & K P Patel

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  1. C D DiNardo
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Correspondence to C D DiNardo.

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DiNardo, C., Jabbour, E., Ravandi, F. et al. IDH1 and IDH2 mutations in myelodysplastic syndromes and role in disease progression. Leukemia 30, 980–984 (2016). https://doi.org/10.1038/leu.2015.211

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