Identification of Novel Alterations in the ASXL1 Gene and Its Expression Profile in CML Patients
Novel Alterations in the ASXL1 Gene and Its Expression Profile in CML Patients
DOI:
https://doi.org/10.54393/pbmj.v8i12.1334Keywords:
Philadelphia Chromosomes, Tyrosine Kinase Inhibitors, Additional Sex Combs Like 1 (ASXL1) Gene , Hematopoietic Stem CellAbstract
Chronic myeloid leukemia is a hematopoietic stem cell malignancy characterized by excessive proliferation of white blood cells, primarily driven by the Philadelphia chromosome (t 9;22). Despite the availability of tyrosine kinase inhibitors, disease progression and therapy resistance remain major challenges, often linked to additional somatic mutations. Objectives: To find out the mutational status and expression variations of the ASXL1 gene hotspot region in CML patients treated by TKIs. Methods: This retrospective cross-sectional study was conducted at the Department of Zoology, Division of Science and Technology, University of Education, Lahore, Pakistan. DNA and mRNA of 50 CML patients were analyzed alongside 10 healthy controls and statistically assessed using SPSS. Results: Results showed that sequence analysis of exon 13 identified hotspot mutations, including two novel missense alterations, G659S and D667E, within the coding region of ASXL1. In-silico analysis also suggested potential structural and functional relevance of these variants. The ASXL1 gene expression showed a progressive but statistically non-significant down-regulation in CML patients across disease phases (p=0.662), disease duration (p=0.42), treatment with second-line versus first-line TKIs (p=0.412), and wild-type and mutant (p=0.544). Conclusions: It is concluded that two novel missense alterations, G6559S and D667E, were identified in the hotspot region, and ASXL1 gene expression was downregulated non-significantly in CML patients.
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