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References
Shlush LI. Age-related clonal hematopoiesis. Blood. 2018;131:496–504.
Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371:2488–98.
Schneider F, Hoster E, Schneider S, Dufour A, Benthaus T, Kakadia PM, et al. Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML). Ann Hematol. 2012;91:9–18.
McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H, Stephens J, et al. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep. 2015;10:1239–45.
Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, et al. Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374:422–33.
Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–21.
Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.
Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371:2477–87.
Patel JL, Schumacher JA, Frizzell K, Sorrells S, Shen W, Clayton A, et al. Coexisting and cooperating mutations in NPM1-mutated acute myeloid leukemia. Leuk Res. 2017;56:7–12.
Mayle A, Yang L, Rodriguez B, Zhou T, Chang E, Curry CV, et al. Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation. Blood. 2015;125:629–38.
Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506:328–33.
Gaidzik VI, Weber D, Paschka P, Kaumanns A, Krieger S, Corbacioglu A, et al. DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia. Leukemia. 2017;32:30–7.
Hollein A, Meggendorfer M, Dicker F, Jeromin S, Nadarajah N, Kern W, et al. NPM1 mutated AML can relapse with wild-type NPM1: persistent clonal hematopoiesis can drive relapse. Blood Adv. 2018;2:3118–25.
Schnittger S, Schoch C, Kern W, Mecucci C, Tschulik C, Martelli MF, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood. 2005;106:3733–9.
Acknowledgements
We thank all patients and clinicians for their participation in this study and all co-workers in our laboratory for their excellent technical assistance.
Author contributions
AH and CH designed the study. LVC and AH interpreted the data and wrote the manuscript. MM, SJ and FD did molecular analyses. SH helped with statistical analysis. TH was responsible for cytomorphologic analyses, CH for cytogenetic and FISH analyses and WK for immunophenotyping. All authors read and contributed to the final version of the manuscript.
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AH, MM, FD, SJ, SH: Employment by MLL Munich Leukemia Laboratory; LVC: grant by Torsten Haferlach Leukämiediagnostikstiftung. CH, WK, TH: Equity ownership of MLL Munich Leukemia Laboratory.
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Part of this work was presented at the 60th annual meeting of the American Society of Hematology, San Diego, CA, December 2018 (abstract #0996).
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Cappelli, L., Meggendorfer, M., Dicker, F. et al. DNMT3A mutations are over-represented in young adults with NPM1 mutated AML and prompt a distinct co-mutational pattern. Leukemia 33, 2741–2746 (2019). https://doi.org/10.1038/s41375-019-0502-0
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DOI: https://doi.org/10.1038/s41375-019-0502-0
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