Bamusa Salem Ahmed, Qureshi Wardah, Gohar Atia, Irfan Muhammad, Khan Ishtiaq Ahmad, Shakeel Muhammad
Ministry of Public Health and Population, Hadhramout, Yemen.
Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi, 75270, Pakistan.
BMC Genom Data. 2025 Jul 12;26(1):49. doi: 10.1186/s12863-025-01324-3.
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.
ASXL1基因是急性髓系白血病（AML）中最常发生突变的基因之一。它与侵袭性体征和不良临床预后相关。本研究的目的是分析ASXL1基因突变的基因谱及其对巴基斯坦AML患者总生存期的影响。招募了38例特征明确的AML患者，使用Illumina NextSeq500下一代测序（NGS）系统对ASXL1进行DNA测序。采用生物信息学工具的标准流程来确定突变谱。将纳入的AML患者的突变谱与千人基因组计划和TCGA AML数据集的突变谱进行比较。分析显示，38例AML患者的ASXL1基因共有43个基因变异（1.13个变异/患者）。在ASXL1基因的第12、13外显子中观察到8个罕见变异。值得注意的是，在两名患者（5.26%）中发现了第13外显子（NM_015338转录本）中一个复发性罕见的非同义有害变异p.G1336S。与ASXL1阴性的AML患者相比，ASXL1阳性（但TP53、FLT3、NPM1、EZH2和WT1阴性）的AML患者总生存期较短（p < 0.05）。此外，本研究中ASXL1阳性AML患者的总生存期与TCGA AML患者的总生存期相当。总之，ASXL1基因的非沉默突变与AML患者较低的生存率相关。建议进行更大样本量队列的进一步研究以供后续临床应用。
