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Acute myeloid leukemia

Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia

Leukemia volume 30, pages 545–554 (2016)Cite this article

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Abstract

We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and ‘simplified analysis of co-mutations’ using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: P<0.0001). In conclusion, CMGAs in AML were found to be strong independent adverse prognostic factors and simplified co-mutation analysis to have clinical usefulness and applicability.

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  1. S Wakita and H Yamaguchi: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Nippon Medical School, Tokyo, Japan

    S Wakita, H Yamaguchi, Y Fujiwara, S Yui, K Fukunaga, T Ryotokuji, T Hirakawa, K Arai, T Kitano, F Kosaka, H Tamai, K Nakayama & K Inokuchi

  2. Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan

    T Ueki

  3. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    K Usuki

  4. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    S Kurosawa & T Fukuda

  5. Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Y Kobayashi & E Kawata

  6. Department of Hematology, Yokohama Minami Kyousai Hospital, Yokohama, Japan

    K Tajika & S Gomi

  7. Department of Gastroenterology, Asahi General Hospital, Chiba, Japan

    M Koizumi

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Correspondence to H Yamaguchi.

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Author contributions

SW and HY were the principal investigators and take primary responsibility for the paper. SW, HY, TU, KU, SK, YK, EK, KT, SG, MK, HT, KN, TF and KI recruited the patients. SW, HY, KA, TK and FK performed the laboratory work for this study. SW, HY, YF, SY, KF, TR, TH and KI analyzed the data and wrote the paper.

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Wakita, S., Yamaguchi, H., Ueki, T. et al. Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia. Leukemia 30, 545–554 (2016). https://doi.org/10.1038/leu.2015.288

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