XIST lncRNA Knockdown Potentiates Dinaciclib-Induced Apoptosis in Acute myeloid leukemia via Bcl-2/NF-κB Axis Suppression

Background Acute myeloid leukemia (AML) is a diverse hematologic cancer marked by the clonal growth of immature hematopoietic cells and genetic abnormalities. Despite advances in chemotherapy, stem cell transplantation, and targeted therapies, patient outcomes continue to be poor because of therapeutic resistance and elevated relapse rates. Emerging research highlights the role of long noncoding RNAs, dysregulated pathways like NF-κB and Bcl-2, and cyclin-dependent kinase inhibitors such as Dinaciclib in overcoming resistance and may inform the creation of more efficient treatment approaches. Methods In this research, we used the Cancer Genome Atlas (TCGA) database for a pan-cancer bioinformatics analysis of XIST, identifying its potential role in AML. XIST siRNA and Dinaciclib were used alone or in combinations, and their apoptosis and anti-proliferation effect was measured by Annexin-V/PI and ELISA. RT-qPCR was used to analyze XIST, Bcl-2, NF-κB, and CDK1, 2, 5, and 9s expression. All procedures were conducted on peripheral blood mononuclear cells (PBMCs) as well as bone marrow mononuclear cells (BMNCs) from 12 patients with AML subtypes M2, M3, M4, and M5 were included. Results Treatment of the AML primary cells (both PBMCs and BMMCs) with anti-XIST siRNA and Dinaciclib has demonstrated a potent synergistic effect on the induction of apoptosis in comparison to untreated AML cells. Inhibition of XIST lncRNA led to decreased AML cell survival by inactivation of NF-κB and Bcl-2 pathways. Conclusion Overall, the innovative combination therapy utilizing Dinaciclib and anti-XIST siRNA has proven to be an effective treatment strategy, successfully inducing apoptosis in malignant AML cells.