Abstract
Hematological malignancies (HM) constitute a variety of cancers originating in blood, bone marrow (BM), and lymphatic systems. During the last two decades, the incidence of HM has dramatically increased worldwide. The etiology of HM is still debatable. Genetic instability is a major risk factor for HM. DDR network is a complex signal transduction cellular machinery that detects DNA damage and activates cellular repair factors, thus maintaining genomic integrity. DDR network detects a variety of DNA damage and triggers the activation of cell cycle control, DNA repair, senescence, and apoptosis. Among the DNA repairing pathways, the DNA damage response (DDR) pathway includes DNA damage signaling apparatus such as ATM and ATR genes. ATM tends to detect double-strand breaks (DSBs) while ATR detects single-strand DNA (ssDNA). The study was conducted to observe the expression deregulations of DNA damage response (DDR) pathway genes (ATM, ATR) at mRNA level in 200 blood cancer patients and 200 controls. The real-time PCR was used to analyze the expression of the target genes. The expression results showed statistically significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) genes in blood cancer patients vs. controls. Moreover, a significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) was obtained in chemotherapy-treated patients vs. healthy controls. The results suggest that dysregulation in ATM and ATR genes may be associated with increased blood cancer risk.
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Acknowledgements
Higher Education Commission of Pakistan (HEC) and CAMSATS University, Islamabad, provided financial and infrastructural support to the authors. The authors thank the patients and the personnel of the Pakistan Institute of Medical Sciences (PIMS) in Islamabad for their participation in study.
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All of the authors read and approved the final version of manuscript. AP, AUK, and AM collected and isolated the RNA samples. AP and AN performed the expression analysis study. AP and IM performed statistical analyses of the data and draft of the manuscript. MAK and IM supervised the project and provided critical revisions. All the authors discussed the results and commented on the manuscript.
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Communicated by Shuhua Xu.
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Parvez, A., Mahjabeen, I., Mehmood, A. et al. Expression variations of DNA damage response genes ATM and ATR in blood cancer patients. Mol Genet Genomics 298, 1173–1183 (2023). https://doi.org/10.1007/s00438-023-02043-z
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DOI: https://doi.org/10.1007/s00438-023-02043-z