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National Academy of Sciences, Proceedings of the National Academy of Sciences, 42(117), p. 26340-26346, 2020

DOI: 10.1073/pnas.2014732117

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Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/ KMT2A

Journal article published in 2020 by Marius Bill ORCID, Krzysztof Mrózek, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Christopher J. Walker, Deedra Nicolet, Dimitrios Papaioannou, James S. Blachly, Shelley Orwick ORCID, Andrew J. Carroll, Jonathan E. Kolitz, Bayard L. Powell, Richard M. Stone, Albert de la Chapelle ORCID, John C. Byrd and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Significance Balanced rearrangements involving 11q23/ KMT2A are among the most frequent chromosomal abnormalities in acute myeloid leukemia (AML). We analyzed the mutational status of 81 genes, clinical features and outcomes of patients with recurring 11q23/ KMT2A rearrangements. We found that mutations in genes of the RAS pathway were most frequent, and that there were differences in mutation patterns among patients with different 11q23/ KMT2A rearrangements. Outcomes of patients age <60 y with t(9;11)(p22;q23)/ KMT2A - MLLT3 , currently classified in the intermediate-risk group of the 2017 European LeukemiaNet classification, were superior to outcomes of intermediate-risk patients without t(9;11). Older patients with t(9;11) and patients with other 11q23/ KMT2A rearrangements had poor outcomes. Our study improves understanding of the mutational landscape and clinical implications for AML patients with 11q23/ KMT2A rearrangements.