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Acute myeloid leukemia

Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML

Leukemia volume 32, pages 295–302 (2018)Cite this article

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Abstract

RUNX1-mutated acute myeloid leukemia (AML) show a distinct pattern of genetic abnormalities and an adverse prognosis. We analyzed the impact of multiple RUNX1 mutations and RUNX1 wild-type (WT) loss in 467 AML with RUNX1 mutations (mut): (1) RUNX1 WT loss (n=53), (2) >1 RUNX1mut (n=94) and (3) 1 RUNX1mut (n=323). In 1 RUNX1mut, +8 was most frequent, whereas in WT loss +13 was the most abundant trisomy (+8: 66% vs 31%, P=0.022; +13: 15% vs 62%, P<0.001). Analyses of 28 genes in 163 selected cases revealed SRSF2 (39%), ASXL1 (36%), DNMT3A (19%), IDH2 (17%) and SF3B1 (17%) as most frequently mutated genes. RUNX1 WT loss showed a higher frequency of ASXL1mut compared with the other cases (50% vs 29%, P=0.009). Median overall survival (OS) in the total cohort was 14 months. WT loss (OS: 5 months) and >1 RUNX1mut (14 months) showed an adverse impact on prognosis compared with 1 RUNX1mut (22 months; P=0.002 and 0.048, respectively). Mutations in ASXL1 and ⩾2 additional mutations correlated with shorter OS (10 vs 18 months, P=0.028; 12 vs 20 months, P=0.017). Thus, the number of RUNX1mut, RUNX1 WT loss and the number and type of additional mutations is biologically and clinically relevant.

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Acknowledgements

We thank all co-workers at the MLL Munich Leukemia Laboratory for approaching together many aspects in the field of leukemia diagnostics and research by their dedicated work. We would like to thank all physicians for providing and caring for patients as well as collecting data.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    A Stengel, W Kern, M Meggendorfer, N Nadarajah, T Haferlach & C Haferlach

  2. MLL2, Praha, Czech Republic

    K Perglerovà

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  1. A Stengel
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Correspondence to A Stengel.

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CH, WK and TH declare part ownership of Munich Leukemia Laboratory (MLL). AS, MM and NN are employed by the MLL Munich Leukemia Laboratory. KP is employed by MLL2.

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Stengel, A., Kern, W., Meggendorfer, M. et al. Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML. Leukemia 32, 295–302 (2018). https://doi.org/10.1038/leu.2017.239

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