Cell Physiol Biochem. 2018 Jun 29;47(5):1853-1861. doi: 10.1159/000491065. [Epub ahead of print]
Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1.
Cheng Z1,2, Dai Y3,4, Pang Y5, Jiao Y6, Zhao H7, Wu S8, Zhang L8, Zhang Y8, Wang X8, Wang L8, Ma D8, Qin T7, Hu N7, Zhang Y9, Hu K2, Zhang Q8,10, Shi J1,11,12, Fu L2,7,13.
Abstract
BACKGROUND/AIMS:
Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1.
METHODS:
Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure.
RESULTS:
Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age ≥60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count ≥50×109/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P< 0.001). Multivariate analysis suggested that allo-HSCT and NPM1 mutations were independent favorable prognostic factors for EFS and OS (all P< 0.05), WBC count ≥50×109/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043).
CONCLUSIONS:
Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT.
© 2018 The Author(s). Published by S. Karger AG, Basel.
KEYWORDS:
Acute myeloid leukemia; M0 and M1; Mutational spectrum; Next generation sequencing; Prognosis
- PMID:
- 29961066
- DOI:
- 10.1159/000491065
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