Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis

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Item Type:	Article
Title:	Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis
Creators Name:	Thol, F., Klesse, S., Köhler, L., Gabdoulline, R., Kloos, A., Liebich, A., Wichmann, M., Chaturvedi, A., Fabisch, J., Gaidzik, V.I., Paschka, P., Bullinger, L., Bug, G., Serve, H., Göhring, G., Schlegelberger, B., Lübbert, M., Kirchner, H., Wattad, M., Kraemer, D., Hertenstein, B., Heil, G., Fiedler, W., Krauter, J., Schlenk, R.F., Döhner, K., Döhner, H., Ganser, A. and Heuser, M.
Abstract:	We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, complete remission (CR) and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal hematopoiesis of indeterminate potential years before AML, older age, secondary AML and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2). In 82% of AML patients with LM-CH, the preleukemic clone was refractory to chemotherapy and was the founding clone for relapse. Both LM-CH and non-LM-CH MRD-positive AML patients who achieved CR had a high risk of relapse after 10 years (75% and 75%, respectively) compared with patients without clonal hematopoiesis in CR with negative MRD (27% relapse rate). Long-term survival of patients with LM-CH was only seen after allogeneic hematopoietic stem cell transplantation (HSCT). We define AML patients with LM-CH as a distinct high-risk group of AML patients that can be identified at diagnosis through mutation analysis in T cells and should be considered for HSCT.
Keywords:	Acute Myeloid Leukaemia, Cancer Genetics, Diagnosis, Haematopoiesis, Haematopoietic Stem Cells
Source:	Leukemia
ISSN:	1476-5551
Publisher:	Nature Publishing Group
Volume:	31
Number:	6
Page Range:	1286-1295
Date:	June 2017
Official Publication:	https://doi.org/10.1038/leu.2016.345
PubMed:	View item in PubMed

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