DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.

DNA damage can alter nucleotide sequences and lead to expression of dysfunctional proteins that impact normal cellular physiology. Sources of DNA damage can be endogenous or exogenous and include reactive oxygen species (ROS) or ionizing radiation [1]. DNA damaging agents can broadly be classified into two different categories: clastogens and aneugens. Clastogens cause chromosomal breaks and induce micronuclei (MN) due to generation of acentric chromosomal fragments. In contrast, aneugens lead to the incorporation of whole chromosomes in MN by generation of aneuploidy that affects cell proliferation and the mitotic spindle apparatus [2].

DNA repair plays an essential role in protecting cells that are repeatedly exposed to endogenous or exogenous insults that can induce varying degrees of DNA damage. Any defect in DNA repair mechanisms results in multiple genomic changes that ultimately may result in mutation, tumor growth, and/or cell apoptosis. Furthermore, impaired repair mechanisms can also lead to genomic instability, which can initiate tumorigenesis and development of hematological malignancy. This review discusses recent findings and highlights the importance of DNA repair components and the impact of their aberrations on hematological malignancies.

(1) Background: Chronic myeloid leukemia is defined as the neoplastic development of mostly myeloid cells in the bone marrow. Several treatments, including chemotherapy, radiation, hormone treatment, and immunological therapy, can be used to control this condition. The therapeutic impact on leukemic individuals varies, and the response to therapy varies between patients due to disease heterogeneity. The primary goal of this study is to compare the effects of single and Imatinib (IM) and Hydroxyurea (HU) combined treatment on hematological parameters and gene expression in CML patients. (2) Methods: This study was conducted on 51 patients, with chronic myeloid leukemia, who were admitted to Al-Basher hospital in Amman, Jordan, for follow-up. Their hematological parameters were checked and gene expression was measured for (BCL2, PP2A, CIP2A, and WT1). (3) Results: The BCL2 gene was found to be less expressed in both IM and (HU + IM) treatments as compared to the HU group alone, while PP2A gene expression was raised. Such a thing indicates that the outcome of the combined therapy method is not ideal, since PP2A activation causes CML cells to move toward the blast crisis stage. Furthermore, CIP2A gene expression revealed that IM and (HU + IM) had the same therapeutic effect and were more successful in CML patients than HU alone. With regards to the treatment effect on hematological parameters, notably in CML patients in later stages, the combination therapy (HU + IM) raised lymphocyte count, indicating a greater response to the treatment. When compared to single medicines, the combination treatment reduced the proportion of neutrophils to normal reference ranges. Platelet counts, on the other hand, dramatically decreased in both IM and (HU + IM). (4) Conclusion: Because the studied genes (BCL2, PP2A, CIP2A, and WT1) are participating in cell proliferation and death, the findings show that the examined genes are significant to understand the efficacy of various therapies. Furthermore, it was found that there was a clear effect of the clinic-based strategic treatment on hematological indicators such as WBCs, lymphocytes, neutrophils, and platelet counts.

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.

Objective: This study assesses microRNA-21 (miR-21) and microRNA-302 (miR-302) levels and examines their association with a nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) gene single nucleotide polymorphism (SNP) in chronic myeloid leukemia (CML) patients, aiming to identify these miRNAs as potential diagnostic biomarkers. The findings could contribute to improved diagnostic and treatment approaches. Subject and Methods: This study involved 65 patients with CML at Al-Basheer Hospital, Amman, Jordan, and 30 healthy controls. Hematological parameters were analyzed via complete blood count. Gene expression was assessed by real-time PCR to analyze miRNA and NF-KB SNPs in patients’ plasma. Results: A highly significant difference (p < 0.0001) was observed, indicating that miR-21 expression was higher in CML patients compared to the controls. miR-302 levels were lower in CML patients. The NF-κB Del/Del genotype was associated with a higher white blood cell count compared to the Ins/Ins and Ins/Del genotypes. Platelet counts varied among the CML patients with three polymorphisms. Conclusion: miR-21 is elevated in CML patients, suggesting an oncogenic role. Our results suggest that miR-302 may serve as a prognostic and diagnostic biomarker. The NF-κB1 gene rs28362491 Del/Del genotype may be associated with an increased risk of CML. Identification of these biomarkers can contribute significantly to improve both diagnosis and treatment strategies.