Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique.

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.

[Consistency Analysis of Gene Mutation Sites of Bone Marrow Tumor DNA and Circulating Tumor DNA in Patients with Myelodysplastic Syndrome].

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-tDNA，BM-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.

Association of Gene Mutations with Response to Arsenic-Containing Compound Qinghuang Powder () in Patients with Myelodysplastic Syndromes.

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.