Gene mutation profile and risk stratification in AML1ETOpositive acute myeloid leukemia based on nextgeneration sequencing.
Oncol Rep
; 42(6): 2333-2344, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31638252
ABSTRACT
Gene mutations play an important role in the development and progression of AML1ETOpositive acute myeloid leukemia (AEAML). Nevertheless, the gene mutation profile in this subtype of leukemia remains unclear. In addition, the clinical and prognostic effects of different mutant genes may be underestimated. In the present study, gene sequencing was conducted at diagnosis and relapse with nextgeneration sequencing (NGS) in 64 patients with newly diagnosed AEAML, and 44/64 (68.8%) patients were found to present with a median of 2 (110) recurrent mutations at diagnosis and 6/11 (54.5%) cases were found to present with genetic alterations at relapse. cKIT mutation was the most common in this cohort, with an incidence of 27/64 (42.2%) at diagnosis, followed by ASXL1 (n=10, 15.6%), MET (n=8, 12.5%), MLH1 (n=6, 9.4%), TET2 (n=5, 7.8%), and FBXW7, TP53 and DNMT3A (n=5, 7.8%). Survival analysis showed that cKIT (exon 8, 17) but not exon 10 adversely affected survival. In addition, ASXL1 and TP53 were poor impact factors for recurrencefree survival (RFS) (P<0.05), and ASXL1, MET, FBXW7 and TP53 had a negative impact on overall survival (OS) (P<0.05). Multivariate analysis showed that cKIT (exon 8, 17) [RFS hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.547.34, P=0.002; OS HR 2.84, 95% CI 1.206.71, P=0.018] and ASXL1 mutations (RFS HR 3.13, 95% CI 1.347.32, P=0.009; OS HR 3.94, 95% CI 1.629.61, P=0.003) were independent adverse factors for survival. Further, comutation of these two genes showed even worse effect on disease outcome. Collectively, additional gene mutations play critical role in AEAML. CKIT and ASXL1 mutations are the two most common mutations in this subtype of leukemia. CKIT (exon 8, 17) but not exon 10, and also the ASXL1 mutation poorly affect the disease outcome of this disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Biomarcadores de Tumor
/
Proteínas de Fusión Oncogénica
/
Medición de Riesgo
/
Subunidad alfa 2 del Factor de Unión al Sitio Principal
/
Secuenciación de Nucleótidos de Alto Rendimiento
/
Proteína 1 Compañera de Translocación de RUNX1
/
Mutación
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article