RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features

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Item Type:	Article
Title:	RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features
Creators Name:	Gaidzik, V.I., Teleanu, V., Papaemmanuil, E., Weber, D., Paschka, P., Hahn, J., Wallrabenstein, T., Kolbinger, B., Köhne, C.H., Horst, H.A., Brossart, P., Held, G., Kündgen, A., Ringhoffer, M., Götze, K., Rummel, M., Gerstung, M., Campbell, P., Kraus, J.M., Kestler, H.A., Thol, F., Heuser, M., Schlegelberger, B., Ganser, A., Bullinger, L., Schlenk, R.F., Döhner, K. and Döhner, H.
Abstract:	We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1 mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1 mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers (ASXL1, IDH2, KMT2A, EZH2), components of the spliceosome complex (SRSF2, SF3B1) and STAG2, PHF6, BCOR. RUNX1 mutations were associated with older age (16–59 years: 8.5%; ⩾60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1 mutations were associated with inferior event-free (EFS, P<0.0001), relapse-free (RFS, P=0.0007) and overall survival (OS, P<0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1 mutations predicted for inferior EFS (P=0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1(mut)/ASXL1(mut) (OS, P=0.004), RUNX1(mut)/SRSF2(mut) (OS, P=0.007) and RUNX1(mut)/PHF6(mut) (OS, P=0.03) did significantly worse, whereas patients with the genotype RUNX1(mut)/IDH2(mut) (OS, P=0.04) had a better outcome. In conclusion, RUNX1-mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.
Keywords:	Acute Myeloid Leukemia, Age Factors, Core Binding Factor Alpha 2 Subunit, Disease-Free Survival, Epigenomics, Mutation, Prognosis, Sex Factors, Spliceosomes, Survival Rate, Young Adult
Source:	Leukemia
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Volume:	30
Number:	11
Page Range:	2160-2168
Date:	November 2016
Additional Information:	Erratum in: Leukemia 30(11):2282.
Official Publication:	https://doi.org/10.1038/leu.2016.126
PubMed:	View item in PubMed

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