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Acute Leukemias

High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome

Leukemia volume 28, pages 1449–1458 (2014)Cite this article

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Abstract

t(8;21)/RUNX1-RUNX1T1-positive acute myeloid leukemia (AML) is prognostically favorable; however, outcome is heterogeneous. We analyzed 139 patients with t(8;21)/RUNX1-RUNX1T1-positive AML (de novo: n=117; therapy-related: n=22) to determine frequency and prognostic impact of additional genetic abnormalities. All patients were investigated for mutations (mut) in ASXL1, FLT3, KIT, NPM1, MLL, IDH1, IDH2, KRAS, NRAS, CBL and JAK2. Sixty-nine of 139 cases (49.6%) had 1 mutation in addition to RUNX1-RUNX1T1, and 23/139 (16.5%) had ⩾2 additional mutations. Most common were KITmut (23/139; 16.5%), NRASmut (18/139; 12.9%) and ASXL1mut (16/139; 11.5%). FLT3-ITD, FLT3-TKDmut, CBLmut, KRASmut, IDH2mut and JAK2mut were found in 2.9–5.0%. Additional chromosomal abnormalities (ACAs) were found in 97/139 (69.8%). Two-year overall survival (OS) was 73.4% in 111 intensively treated patients. KITD816mut negatively impacted on OS in de novo AML (2-year OS: 59.1% vs 82.0%, P=0.03), ASXL1mut on EFS (de novo AML: 20% vs 59.1%, P=0.011; total cohort: 28.6% vs 56.7%, P=0.021). Sex chromosome loss was favorable (2-year EFS: 66.9% vs 43.0%, P=0.031), whereas +8 was adverse on EFS (2-year EFS: 26.7% vs 55.9%, P=0.02). In conclusion, t(8;21)/RUNX1-RUNX1T1-positive AML shows a high frequency of additional genetic alterations. Investigation for KITD816 and ASXL1mut combined with investigation of ACAs is recommended in t(8;21)/RUNX1-RUNX1T1-positive AML because of the prognostic significance of these parameters.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    M-T Krauth, C Eder, T Alpermann, U Bacher, N Nadarajah, W Kern, C Haferlach, T Haferlach & S Schnittger

  2. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria

    M-T Krauth

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  1. M-T Krauth
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Correspondence to S Schnittger.

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SS, WK, CH and TH are part owners of the MLL Munich Leukemia Laboratory GmbH. MTK, CE, TA, UB and NN are employed by the MLL Munich Leukemia Laboratory GmbH.

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Author contributions

SS and MTK were the principal investigators of this study, analyzed the data and wrote the manuscript. CE did analysis of molecular mutations. CH was responsible for chromosome banding analysis. WK was responsible for immunophenotyping and was involved in the statistical analysis. TH was responsible for cytomorphologic analysis, and MTK and UB contributed to cytomorphologic analysis. TA collected and analyzed clinical data. UB contributed writing of the manuscript. NN contributed to statistics and graphics. All authors read and contributed to the final version of the manuscript.

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Krauth, MT., Eder, C., Alpermann, T. et al. High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome. Leukemia 28, 1449–1458 (2014). https://doi.org/10.1038/leu.2014.4

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