c-FLIP and microRNA 708-5p gene expression in newly diagnosed and chemotherapy in acute myeloid leukemia of Iraqi patient

Abstract

Abstract: BACKGROUND: C-FLICE-like inhibitory protein (c-FLIP) is a protein that does not merely block apoptosis signaling but also adjusts further pathways of cell death. Acute myeloid leukemia (AML), a nonhomogeneous hematologic malignancy, is the highly common form of AML among adults and is described through the clonal enlargement of myeloid blasts in the bone marrow (BM), peripheral blood, and/or else tissues. OBJECTIVES: The aims of this study were to investigate the role of c-FLIP and microRNA (miRNA) 708-5p as a prospective prognostic biomarker as well as the therapeutic goal in AML. PATIENTS MATERIALS AND METHODS: This study includes two groups of patients (40) individuals newly diagnosed AML patients, (20) AML taking chemotherapy, and (50) apparently healthy volunteers. The study was conducted at the National Center of Hematology/Mustansiriyah University. The methods employed in the analysis include total RNA extraction, complementary cDNA synthesis, and quantitative real-time polymerase chain reaction (PCR) were used to evaluate the gene expression of cFLIP and miRNA-708-5p. Complete blood count to estimate some hematological parameters. RESULTS: The expression of c-FLIP was notably higher in both newly diagnosed and patients under chemotherapy compared to controls with fold expression (3.291 and 2.92), respectively, with a highly significant (P = 0.0001). The increase in miRNA 708-5p expression in newly diagnosed patients with fold expression (5.345), whereas downregulation in patients under chemotherapy with fold expression (0.789) indicates that treatment may restore its levels, contributing to the suppression of c-FLIP and promoting apoptosis. CONCLUSION: The c-FLIP and miRNA708-5p gene might be used as a biological marker for the AML initial diagnosis. The researches emphasize the role of miRNA 708-5p as a tumor suppressor, which negatively regulates the antiapoptotic protein c-FLIP, indicating its potential as a therapeutic target in AML treatment. By modulating the levels of miRNA708-5p, it may be possible to regulate the expression of c-FLIP, thus enhancing the effectiveness of apoptosis-inducing therapies. This suggests the promising development of miRNA-based therapies as part of AML treatment strategies. Furthermore, miRNA 708-5p can act as a prognostic indicator in AML, with its expression levels offering valuable insights into disease progression and patient response to treatment. Further research into miRNA 708-5p can lead to a better understanding of its role in AML pathogenesis and its potential applications in clinical practice.