1. Genetic evidence for predisposition to acute leukemias due to a missense mutation (p.Ser518Arg) in ZAP70 kinase: a case-control study.
- Author
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Khashei Varnamkhasti, Khalil, Khashei Varnamkhasti, Samire, Shahrouzian, Atefeh, Rahimzadeh, Masoomeh, Naeimi, Leila, Naeimi, Behrouz, and Naeimi, Sirous
- Subjects
SINGLE nucleotide polymorphisms ,LYMPHOBLASTIC leukemia ,ACUTE leukemia ,ACUTE myeloid leukemia ,MISSENSE mutation - Abstract
Background: The apparent lack of additional missense mutations data on mixed-phenotype leukemia is noteworthy. Single amino acid substitution by these non-synonymous single nucleotide variations can be related to many pathological conditions and may influence susceptibility to disease. This case-control study aimed to unravel whether the ZAP70 missense variant (rs104893674 (C > A)) underpinning mixed-phenotype leukemia. Methods: The rs104893674 was genotyped in clients who were mixed-phenotype acute leukemia-, acute lymphoblastic leukemia- and acute myeloid leukemia-positive and matched healthy controls, which have been referred to all major urban hospitals from multiple provinces of country- wide, IRAN, from February 11' 2019 to June 10' 2023, by amplification refractory mutation system-polymerase chain reaction method. Direct sequencing for rs104893674 of the ZAP70 gene was performed in a 3130 Genetic Analyzer. Results: We found that the AC genotype of individuals with A allele at this polymorphic site (heterozygous variant-type) contribute to the genetic susceptibility to acute leukemia of both forms, acute myeloid leukemia and acute lymphoblastic leukemia as well as with a mixed phenotype. In other words, the ZAP70 missense variant (rs104893674 (C > A)) increases susceptibility of distinct cell populations of different (myeloid and lymphoid) lineages to exhibiting cancer phenotype. The results were all consistent with genotype data obtained using a direct DNA sequencing technique. Conclusion: Of special interest are pathogenic missense mutations, since they generate variants that cause specific molecular phenotypes through protein destabilization. Overall, we discovered that the rs104893674 (C > A) variant chance in causing mixed-phenotype leukemia is relatively high. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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