The Correlation Of Gene Mutation And Prognosis And Next Generation Sequencing In Acute Leukemia

Leukemia is a haematopoietic tumor with diversity of clinical manifestations and easy to relapse and metastasis.At the molecular level,leukemia is due to non-hereditary somatic gene mutation accumulation in hematopoietic stem cell,which lead to differentiation abnormal block.Genetic heterogeneity is one of the significant molecular biological characteristics of acute leukemia,including different types of molecular biology abnormalities such as chromosome translocation,inversion,deletion and gene point mutation.Although chemotherapy and allogeneic hematopoietic stem cell transplantation have been widely used in the treatment of acute leukemia and made some progress,clonal evolution caused by somatic mutation is still one of the main reasons for chemotherapy resistance and relapse.Accurately deciphering the mutational profile of leukemia is essential for prognosis prediction,diagnosis and targeted drug selection.With the development of sequencing technology,more and more chromosomal abnormalities and acute leukemia-related gene mutations have been identified.In recent years,more and more gene mutations have been found in acute leukemia patients using high-throughput sequencing technology,but there are still lack of enough specific molecular markers for a large number of acute leukemia patients.In this study,we followed up 206 AML patients and 164 adult B-cell lymphocytic leukemia patients with hematopoietic stem cell transplantation after chemotherapy remission and analyzed the gene mutations with prognosis.It was found that patients with FLT3-ITD and DNMT3 A R882 double mutations and IKZF1 gene mutation were clinically higher in white blood cells and lower complete rate of remission.All patients with FLT3-ITD and DNMT3 A R882 double mutations showed a higher 2-year cumulative recurrence rate and a lower 2-year overall survival and leukemia-free survival after allogeneic hematopoietic stem cell transplantation.Multivariate analysis showed that FLT3-ITD and DNMT3 A R882 double mutations 、IKZF1 gene mutation could be used as independent risk factors for allogeneic hematopoietic stem cell transplantation.Next,we established a probe capture based approach for the detection of acute leukemia mutations profiles followed by high-throughput sequencing.It could be easily distinguish germline mutations and somatic mutations by detecting mutations in nail DNA and bone marrow DNA.Sequencing data of 50 patients with acute leukemia showed that AML-ETO,MLL-AF4,KRAS,NRAS and FLT3 somatic mutations were found in the newly diagnosed leukemia patients,indicating that these mutations could be used as indicators of MRD.In addition,we used the capture chip to analyze the mutations in 7 patients with JMML.According to clinical manifestations and gene mutation profiles,we determined the patient’s treatment program,which avoided unnecessary hematopoietic stem cell transplantation.Our study identified the independent risk predictors of FLT3-ITD and DNMT3 A R882 double mutations and IKZF1 as AML and B adult lymphocytic leukemia by analyzing the relationship between gene mutation and prognosis in patients with acute leukemia and established a new method based on high-throughput sequencing of multi-gene combined analysis of leukemia.It is important for the clinical prognostic stratification of acute leukemia and targeting drug selection and provides a new tool for clinical and scientific research of leukemia.