Role of Sirtuins in the Pathobiology of Onco-Hematological Diseases: A PROSPERO-Registered Study and In Silico Analysis

SIMPLE SUMMARY: The aging of the hematological system can cause physiological disorders such as anemia, reduced immunity, and the increased incidence of blood cancer. Patients diagnosed with hematologic malignancies comprise nearly 10% of all cancer deaths identified in international epidemiologic studies. Therefore, it is considered a public health problem worldwide. Scientific evidence demonstrates the important involvement of sirtuins (SIRTs) in the pathogenesis of several types of solid tumors. However, the role of SIRTs in the pathobiology of malignant hematological diseases has not yet been systematically reviewed. In this systematic review, we highlight the role of different SIRTs in the pathogenesis of acute and chronic leukemias, lymphoma and myeloma. Also, we performed a bioinformatic analysis to identify whether the expression of SIRTs is altered in onco-hematological diseases, such as lymphomas and leukemias. The advent of new applicability of SIRTs in the process of aging and hematological carcinogenesis may allow the development of new diagnostic and therapeutic approaches for these diseases. ABSTRACT: The sirtuins (SIRT) gene family (SIRT1 to SIRT7) contains the targets implicated in cellular and organismal aging. The role of SIRTs expression in the pathogenesis and overall survival of patients diagnosed with solid tumors has been widely discussed. However, studies that seek to explain the role of these pathways in the hematopoietic aging process and the consequences of their instability in the pathogenesis of different onco-hematological diseases are still scarce. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42022310079) and in silico analysis (based on GEPIA database) to discuss the role of SIRTs in the advancement of pathogenesis and/or prognosis for different hematological cancer types. In summary, given recent available scientific evidence and in silico gene expression analysis that supports the role of SIRTs in pathobiology of hematological malignances, such as leukemias, lymphomas and myeloma, it is clear the need for further high-quality research and clinical trials that expands the SIRT inhibition knowledge and its effect on controlling clonal progression caused by genomic instability characteristics of these diseases. Finally, SIRTs represent potential molecular targets in the control of the effects caused by aging on the failures of the hematopoietic system that can lead to the involvement of hematological neoplasms.