Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis

Item Type:	Article
Title:	Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis
Creators Name:	Thol, F. and Klesse, S. and Köhler, L. and Gabdoulline, R. and Kloos, A. and Liebich, A. and Wichmann, M. and Chaturvedi, A. and Fabisch, J. and Gaidzik, V.I. and Paschka, P. and Bullinger, L. and Bug, G. and Serve, H. and Göhring, G. and Schlegelberger, B. and Lübbert, M. and Kirchner, H. and Wattad, M. and Kraemer, D. and Hertenstein, B. and Heil, G. and Fiedler, W. and Krauter, J. and Schlenk, R.F. and Döhner, K. and Döhner, H. and 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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