Journal
LEUKEMIA
Volume 31, Issue 6, Pages 1286-1295Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2016.345
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Funding
- Braukmann-Wittenberg-Herz-Stiftung
- Deutsche Forschungsgemeinschaft
- German Federal Ministry of Education and Research [01EO0802]
- Deutsche Krebshilfe [110284, 110287, 110292, 111267]
- Deutsche Jose Carreras Leukamie-Stiftung e.V [DJCLS R13/14]
- DFG [HE 5240/5-1, HE 5240/6-1, BU 1339/8-1]
- ERC grant under the European Union's Horizon 2020 research and innovation program [638035]
- Dieter-Schlag Stiftung
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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.
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