Iranian journal of Pediatric Hematology and Oncology

en Overexpression of CHK1 and CHK2 in pediatric patients of B-acute lymphoblastic leukemia قلب Heart پژوهشي Research <div style="border:double windowtext 1.5pt; padding:1.0pt 4.0pt 1.0pt 4.0pt">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.</div> Acute lymphoblastic leukemia, Checkpoint kinase 1, Checkpoint kinase 2 233 240 http://ijpho.ssu.ac.ir/browse.php?a_code=A-10-806-2&slc_lang=en&sid=1 Farshad Heidari farshadheydari72@gmail.com 0000-0003-0477-5711 No Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Faranoush faranoushm@iums.ac.ir 0000-0002-2775-2347 No Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran Ali Amini aminia2020@gmail.com 0000-0002-8759-6120 No Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Elahe Rahimian elahee.rahimian@gmail.com 0000-0001-9162-5396 No Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Kamyar Kazemi a.kazemi32@gmail.com No School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mostafa Paridar mstparidar@gmail.com No Ministry of Health and Medical Education, Deputy of Management and Resources Development, Tehran, Iran Ministry of Health and Medical Education, Deputy of Management and Resources Development, Tehran, Iran Majid Safa safa.m@iums.ac.ir 0000-0003-0070-6620 Yes Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran