Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis

被引：44

作者：

Thol, F. ^{[1
]}

Klesse, S. ^{[1
]}

Koehler, L. ^{[1
]}

Gabdoulline, R. ^{[1
]}

Kloos, A. ^{[1
]}

Liebich, A. ^{[1
]}

Wichmann, M. ^{[1
]}

Chaturvedi, A. ^{[1
]}

Fabisch, J. ^{[1
]}

Gaidzik, V. I. ^{[2
]}

Paschka, P. ^{[2
]}

Bullinger, L. ^{[2
]}

Bug, G. ^{[3
]}

Serve, H. ^{[3
]}

Goehring, G. ^{[4
]}

Schlegelberger, B. ^{[4
]}

Luebbert, M. ^{[5
]}

Kirchner, H. ^{[6
]}

Wattad, M. ^{[7
]}

Kraemer, D. ^{[8
]}

Hertenstein, B. ^{[9
]}

Heil, G. ^{[10
]}

Fiedler, W. ^{[11
]}

Krauter, J. ^{[12
]}

Schlenk, R. F. ^{[2
]}

Doehner, K. ^{[2
]}

Doehner, H. ^{[2
]}

Ganser, A. ^{[1
]}

Heuser, M. ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Univ Ulm, Dept Internal Med 3, Ulm, Germany

[3] Goethe Univ Frankfurt, Dept Internal Med 3, Frankfurt, Germany

[4] Hannover Med Sch, Inst Cell & Mol Pathol, Hannover, Germany

[5] Univ Freiburg, Med Ctr, Dept Hematol Oncol, Freiburg, Germany

[6] Krankenhaus Siloah, Dept Internal Med 3, Hannover, Germany

[7] Evangel Krankenhaus Essen Werden, Essen, Germany

[8] Klinikum Oldenburg, Oldenburg, Germany

[9] Klinikum Bremen Mitte, Bremen, Germany

[10] Klinikum Ludenscheid, Dept Internal Med 5, Ludenscheid, Germany

[11] Hubertus Wald Univ, Canc Ctr, Univ Hosp Hamburg Eppendorf, Dept Med 2,Oncol Ctr, Hamburg, Germany

[12] Klinikum Braunschweig, Dept Hematol & Oncol, Braunschweig, Germany

来源：

LEUKEMIA | 2017年 / 31卷 / 06期

基金：

欧盟地平线“2020”;

关键词：

DNMT3A MUTATIONS; SOMATIC MUTATIONS; STEM-CELLS; AML; ORIGIN; MUTANT; EVOLUTION; THERAPY; IMPACT; ADULTS;

D O I：

10.1038/leu.2016.345

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1286 / 1295

页数：10

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