Overexpression of CHK1 and CHK2 in pediatric patients of B-acute lymphoblastic leukemia

Abstract

Background: Despite breakthroughs in the development of chemotherapy drugs to treat pediatric B-acute lymphoblastic leukemia (B-ALL), the relapse rate remains a major therapeutic challenge, requiring more detailed characterization of molecular elements underlying disease development and resistance to treatment. Checkpoint kinase 1 (CHK1) and checkpoint kinase 2 (CHK2) are two critical mediators of the DNA damage response (DDR) mechanism that activate the downstream components responsible for DNA repair, cell cycle regulation, and apoptosis. It has been shown that altered expression of CHK1 and CHK2 in various tumor entities promotes tumorigenesis and disease progression.

Materials and Methods: In this case-control study, we evaluated the relative expression status of CHK1 and CHK2 genes in pediatric B-ALL patients at diagnosis (n=20), during complete remission (n=23) and relapse phase (n=10), as well as 20 peripheral blood samples from healthy children as a normal control group. The mRNA expression levels of CHK1 and CHK2 were determined by the Real-time PCR method. Data were compared using the Mann–Whitney U test for the relative expression level of target mRNA in different phases of B-ALL. Data were presented as median and statistical significance was described as a P-value less than 0.05.

Results: Our results revealed that CHK1 expression increased in newly diagnosed patients than in healthy individuals (p ≤ 0.001). Relapsed patients had higher CHK1 expression than the newly diagnosed (p ≤ 0.05) and complete remission (p ≤ 0.001) counterparts. CHK2 was overexpressed in all phases of the diseases (p ≤ 0.001) without any significant alteration among the studied groups.

Conclusion: Given the CHK1 ability to endow cancer cells with a survival advantage upon chemotherapy, the present study suggests it as a potentially promising target in the fight against B-ALL.