Abstract

Age-related somatic mutations linked to clonal hematopoiesis have been found in apparently healthy individuals and increase the risk of developing hematologic malignancies. In acute myeloid leukemia (AML) the clinical relevance of clonal hematopoiesis remains controversial and data on patients with detectable clonal hematopoiesis, consolidated with hematopoietic stem cell transplantation are limited. We analyzed samples from 113 AML patients in complete remission prior to hematopoietic stem cell transplantation for the presence of clonal hematopoiesis-associated mutations. The results were correlated with clinical and biological data. In complete remission we found 75 mutations previously linked to clonal hematopoiesis in 47 patients (41.6%). Twenty patients had ≥2 mutations linked to clonal hematopoiesis. DNMT3A, TET2, and ASXL1 were most frequently mutated. When compared to pre-treatment samples we found variable patterns of mutation persistence depending on the gene mutated. In AML patients after allogeneic hematopoietic stem cell transplantation the presence of clonal hematopoiesis-associated mutations in complete remission did not associate with inferior clinical outcome. This study demonstrates that clonal hematopoiesis is a frequent phenomenon in AML patients. Presence of clonal hematopoiesis has no negative prognostic impact in the context of an allogeneic hematopoietic stem cell transplantation and might be beneficial if certain genes are affected.

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Acknowledgements

This work was supported by the Deutsche José-Carreras-Stiftung (#04R/2016 and #PS15/05 J.G.), Verein zusammen gegen den Krebs e.V., and Ein Herz für Kinder e.V. The authors thank Janet Bogardt, Annette Jilo, Dagmar Cron, Ines Kovacs, Kathrin Wildenberger, Scarlett Schwabe, Christine Günther, Daniela Bretschneider, Evelin Hennig, and Christel Müller for their assistance. The authors like to acknowledge Prof. Ralf Burckhardt and Dr. Max Hubmann for support in data collection.

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  1. Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany

    • Juliane Grimm
    • , Marius Bill
    • , Madlen Jentzsch
    • , Stefanie Beinicke
    • , Janine Häntschel
    • , Karoline Goldmann
    • , Julia Schulz
    • , Michael Cross
    • , Georg–Nikolaus Franke
    • , Gerhard Behre
    • , Vladan Vucinic
    • , Wolfram Pönisch
    • , Thoralf Lange
    • , Dietger Niederwieser
    •  & Sebastian Schwind

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Correspondence to Sebastian Schwind.

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https://doi.org/10.1038/s41409-018-0413-0