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Leukemia. 2018 Dec;32(12):2536-2545. doi: 10.1038/s41375-018-0147-4. Epub 2018 Jun 5.

NF1 mutations are recurrent in adult acute myeloid leukemia and confer poor outcome.

Author information

1
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. ann-kathrin.eisfeld@osumc.edu.
2
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
3
Alliance for Clinical Trials in Oncology Statistics and Data Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
4
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. krzysztof.mrozek@osumc.edu.
5
Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
6
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
7
Department of Internal Medicine, The Comprehensive Cancer Center of Wake Forest University, Wake Forest University, Winston-Salem, NC, USA.
8
Monter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY, USA.
9
Roswell Park Cancer Institute, Buffalo, NY, USA.
10
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
11
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. clara.bloomfield@osumc.edu.

Abstract

Targeted mutation assessment of 81 genes in 1021 adults with de novo acute myeloid leukemia (AML) identified recurrent mutations in the neurofibromin 1 (NF1) gene in 52 (5.1%) patients, including 36 (5.2%) younger and 16 (4.8%) older patients, which suggests NF1 belongs to the 20 most frequently mutated genes in adult AML. NF1 mutations were found throughout the gene, and comprised missense, frameshift, and nonsense mutations. One mutation hotspot, at amino acid threonine 676 (Thr676), was found in 27% of AML patients with NF1 mutations. NF1-mutated patients belonged more often to the adverse European LeukemiaNet (ELN) risk category than NF1 wild-type patients. Among patients aged <60 years, the presence of NF1 Thr676 mutations was associated with lower complete remission (CR) rates (P = 0.04) and shorter overall survival (OS; P = 0.01), as was the presence of any NF1 mutation in patients in the adverse ELN risk category (CR, P = 0.05; OS, P < 0.001). CR rates were also lower in NF1-mutated patients aged ≥60 years compared with NF1 wild-type patients (P = 0.001). In summary, our findings provide novel insights into the frequency of NF1 mutations in AML, and are suggestive of an adverse prognostic impact in patients treated with standard chemotherapy.

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