Abstract
The ASXL1 gene is one of the most frequently mutated genes in acute myeloid leukemia (AML). It is associated with signs of aggressiveness and adverse clinical outcomes. The aim of the current study was to analyze the genetic profile of ASXL1 gene mutations and its impact on the overall survival in AML patients from Pakistan.Thirty-eight well characterized AML patients were enrolled, and DNA sequencing of the ASXL1 was performed using the Illumina NextSeq500 next generation sequencing (NGS) system. Standard pipeline of bioinformatics tools was used to determine the mutational profile. The mutational profile of the enrolled AML patients was compared with that of 1000 Genomes project, and TCGA AML datasets.The analysis revealed 43 genetic variants in ASXL1 across the 38 AML patients (1.13 variant/patient). Eight rare variants were observed in exons 12, 13 of the ASXL1 gene. Notably, a recurrent rare nonsynonymous deleterious variant p.G1336S in exon 13 (NM_015338 transcript) was found in two patients (5.26%). The overall survival of the ASXL1+ (but TP53, FLT3, NPM1, EZH2, and WT1 negative) AML was shorter compared with the ASXL1- (p < 0.05). Further, the overall survival of current study ASXL1 + AML was found comparable with that of the TCGA AML.In conclusion, the non-silent mutations in ASXL1 were associated with lower survival in AML. Further studies with larger cohort are suggested for subsequent clinical implementation.