[Prognostic value of KIT and other clonal genetic mutations in core-binding factor acute myeloid leukemia].
Zhonghua Xue Ye Xue Za Zhi
; 42(8): 646-653, 2021 Aug 14.
Article
em Zh
| MEDLINE
| ID: mdl-34547870
ABSTRACT
Objective:
To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy.Methods:
The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1(+) AML and 56 patients with CBFß-MYH11(+) AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis.Results:
The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFß-MYH11(+) AML than in those with RUNX1-RUNXIT1 (+) AML (P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1(+) AML, did not affect DFS (P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1(+) AML (P<0.001) , and allo-HSCT significantly prolonged DFS in these patients (P=0.010) .Conclusions:
KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1(+) AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Transplante de Células-Tronco Hematopoéticas
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Proteínas Proto-Oncogênicas c-kit
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Humans
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Middle aged
Idioma:
Zh
Revista:
Zhonghua Xue Ye Xue Za Zhi
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China