Differential diagnosis of hematologic diseases is a huge challenge and advances in genetic studies have made it possible to unravel the many gene interactions in these diseases. In this study, we performed a literature search on the roles of the TP53BP2, BCL2L11, SOD2 and CAT genes in cellular regulatory processes and mechanisms and describe the implications reported in the literature in association with hematologic diseases.

This is an integrative review of the literature from the last 10 years (2015-2024), carried out on the PubMed and Google Scholar platforms, using the following keywords: “hematological diseases”, “implications”, “gene expression”, “polymorphisms”, also using NCBI GENE. Of the total of 87 articles found, only 22 aimed at and covered the clinical focus of the hypothesis of this review.

Several genetic alterations and mutations were described in these genes, with emphasis on individualized SNPs as factors predominantly involved in the development and progression of hematologic malignancies. Most of these highlighted the suppression and silencing of the TP53BP2 and BCL2L11 genes, which play a crucial role in cell death. Oncogenic splice variants (ASPP2k) stood out influencing gene expression, downregulation and interactions with nuclear viral antigens, all of which converge to the deregulation of the apoptosis mechanism, implying susceptibility, proliferation, invasiveness, resistance to treatment and a marker of unfavorable prognosis. In addition, polymorphisms in SOD2 (rs4880) directly contribute to vascular and cerebral damage and complications in sickle cell anemia patients; in addition to being associated with hepatotoxicity in ALL patients; Another SOD2 SNP (rs8031) has been implicated in many studies of patients with refractory AML due to increased resistance to treatment. The SNP rs1001179 in the CAT gene is involved in the dysregulation of antioxidant mechanisms, being correlated with a more aggressive course in CLL patients.

Altered expression of genes involved in apoptotic regulation is frequently associated with several types of cancer and notably contributes to cell proliferation and resistance to chemotherapy, due to impaired apoptosis specifically in multiple myeloma where reduced gene expression has been observed. The diversity and complexity of hematologic malignancies demonstrate the need for an individualized understanding of the underlying causes. Altered gene expression, downregulation, and polymorphisms of many genes suggest the possibility of delineating populations susceptible to the disease to propose an early approach, in addition to suggesting a possible prediction of severity and response to treatment.

Discoveries in these genes may expand early diagnosis, predict disease course, and individualized adaptations in therapy. In this review, we explore the importance of genes that are critical in the pathogenesis, progression, and are potentially essential in the treatment of hematologic malignancies. This study highlights the importance of genetic understanding in the study of large populations, and we believe that the integration of these genetic and molecular discoveries presupposes the transformation of the management of these diseases.