Gene mutational pattern and expression level in 560 acute myeloid leukemia patients and their clinical relevance

Abstract

BackgroundCytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML.MethodsIn this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1.ResultsCertain gene expression levels were associated with the cytogenetic aberration of the disease, especially for MECOM, MEIS1 and BAALC. FLT3, C-KIT and NRAS mutations contained conversed expression profile regarding MEIS1, WT1, GATA2 and BAALC expression, respectively. FLT3, DNMT3A, NPM1 and biallelic CEBPA represented the mutations associated with the prognosis of AML in our group. Higher MECOM and MEIS1 gene expression levels showed a significant impact on complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) both in univariate and multivariate analysis, respectively; and an additive effect could be observed. By systematically integrating gene mutational status results and gene expression profile, we could establish a more refined system to precisely subdivide AML patients into distinct prognostic groups.ConclusionsGene expression abnormalities contained important biological and clinical informations, and could be integrated into current AML stratification system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1279-4) contains supplementary material, which is available to authorized users.

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

“…AML is a kind of hematopoietic neoplasm with high heterogeneity, which is reflected by complex cytogenetic changes and molecular genetic aberrancy. 31 AML patients were divided into three risk groups based on the NCCN F I G U R E 4 Kaplan-Meier curves for OS stratified by the mutation status determined by DNMT3A, FLT3, and NPM1 genes. Lines in different colors represent the survival of patients in different groups, respectively.…”

“…AML is a kind of hematopoietic neoplasm with high heterogeneity, which is reflected by complex cytogenetic changes and molecular genetic aberrancy 31 . AML patients were divided into three risk groups based on the NCCN guideline: low‐risk cytogenetics, intermediate‐risk cytogenetics and high‐risk cytogenetics 6 .…”

Polymorphisms of the CYR61 gene in patients with acute myeloid leukemia in a Han Chinese population

“…CEBPA , c-Kit , FLT3 , DNMT3A , NPM , ASXL1 , U2AF1 , and SRSF2 mutations are used in clinical practice and affect the diagnosis, stratification, and treatment of AML. [ 2 , 18 ] Combined with the data from ANLN clinical tests and RNA-seq, we speculated that there were relationships between these mutations and Cyr61 polymorphisms, but no correlations were found. Furthermore, we analyzed the distributions of rs2297141 and rs6576776 polymorphisms in the subtypes of AML.…”

“…The mutations in AML genes ( c-kit , FLT3-TKD , CEBPA , NPM1 , DNMT3A , U2AF1 , SRSF2 , ASXL1 ), which play crucial roles in the diagnosis, stratification, and treatment of AML, [ 2 , 3 , 17 , 18 ] were analyzed with Sanger sequencing: DNA was amplified for the genes (c-kit, FLT3-TKD, CEBPA, NPM1, DNMT3A, U2AF1, SRSF2, ASXL1) with S1000 Thermal Cycler, then amplified products were analyzed with 3730xl DNA Analyzer (Thermo Fisher Scientific, Waltham).…”

WT-1, BAALC, and ERG Expressions in Iranian Patients with Acute Myeloid Leukemia Pre- and Post-chemotherapy

“…5 High expression of WT-1 in acute leukemia has been reported to represent a molecular marker of malignant hematopoiesis and was associated with fewer remissions and poor overall survival. 6,7 Another molecular change in AML is the deregulated expression of brain and acute leukemia-cytoplasmic (BAALC) gene. BAALC, which maps on chromosome 8 at 8q22.3, is involved in neuroectodermal and hematopoietic development.…”