lunes, 9 de julio de 2018

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1. - PubMed - NCBI

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1. - PubMed - NCBI



 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 Z1,2Dai Y3,4Pang Y5Jiao Y6Zhao H7Wu S8Zhang L8Zhang Y8Wang X8Wang L8Ma D8Qin T7Hu N7Zhang Y9Hu K2Zhang Q8,10Shi J1,11,12Fu 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.

KEYWORDS:

Acute myeloid leukemia; M0 and M1; Mutational spectrum; Next generation sequencing; Prognosis

PMID:
 
29961066
 
DOI:
 
10.1159/000491065
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