RESUMO
To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next-generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3-internal tandem duplication (FLT3-ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPAdouble mutation . In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse-free survival (RFS), DNMT3A, FLT3-ITD, or RUNX1 mutation predicted a higher likelihood of remission-induction failure, whereas NRAS mutation or CEBPAdouble mutation predicted longer OS. Concurrent DNMT3A, FLT3-ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation-related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.
Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Leucemia Mieloide Aguda/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Pequim , Feminino , Predisposição Genética para Doença , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To investigate the relationship between gene mutations and response to Compound Qinghuang Powder (, CQHP) in patients with myelodysplastic syndrome (MDS). METHODS: Forty-three MDS patients were genotyped by ultra-deep targeted sequencing and the clinical data of patients were collected and the relationship between them was analyzed. RESULTS: Up to 41.86% of patients harbored genet mutations, in most cases with more than one mutation. The most common mutations were in SF3B1, U2AF1, ASXL1, and DNMT3A. After treatment with CQHP, about 88.00% of patients no longer required blood transfusion, or needed half of prior transfusions. CONCLUSIONS: CQHP is an effective treatment for patients with MDS, especially those with gene mutations in SF3B1, DNMT3A, U2AF1, and/or ASXL1.
Assuntos
Arsênio/uso terapêutico , Arsenicais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Estudos de Associação Genética , Mutação/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Adulto , Transfusão de Sangue , Feminino , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the consistency of gene mutation sites between bone marrow DNA (BM-tDNA) and perepheral plasma circulating tumor DNA (PP-ctDNA) in patients with myelodysplastic syndrome (MDS). METHODS: The simultaneous sampled BM and PP from 19 patients (SBPP) was detected by NGS-127 gene panel, and the consistency of VAF between BM-tDNA and PP-ctDNA was analyzed. The peripheral blood cell tumor DNA (PC-tDNA) of 5 out of 19 patients was detected randomly, the consistency of VAF among PC-tDNAï¼BM-tDNA and PP-ctDNA was analyzed. The non simultaneous sampled BM and PP from 13 patients (NBPP) was detected, and the difference value of VAF between BM-tDNA and PP-ctDNA in SBPP and NBPP was analyzed. RESULTS: The average concentration of PP-ctDNA in SBPP was 0.59 ng/µl and 0.604 ng/µl in NBPP. The median concentration of PP-ctDNA in SBPP and NBPP was 0.330 ng/µl and 0.338 ng/µl, respectively. The study showed a good consistency of VAF between BM-tDNA and PP-ctDNA in the SBPP (R2=0.9693, P<0.05), and the consistency of VAF between BM-tDNA and PP-ctDNA in single base replacement (SNP) sites (R2=0.9712) was better than that in insertion deletion (Indel) sites (R2=0.6813). The results showed a good consistency of VAF between BM-tDNA and PP-ctDNA both in 12 patients before treatment (R2=0.9325, P<0.05) and 5 patients (R2=0.9875, P<0.05) after treatment. The results also showed that the VAF of PC-tDNA had a good consistency with the VAF of BM-tDNA (R2=0.8783) and PP-ctDNA (R2=0.8783) (P<0.05). The difference value of VAF between BM-tDNA and PP-ctDNA in SBPP was significantly lower than that in NBPP (P<0.05). CONCLUSION: PP can replace BM as a biological sample for genes mutation detection in patients with MDS due to its stable concentration, high degree of consistency with bone marrow in clinical significant mutation sites and easy collection.