AML-019: Nexus of Apoptosis Repressor with Caspase Recruitment Domain, Potassium and Calcium in Acute Myeloid Leukemia

Context and Objective: Acute myeloid leukemia (AML) is a malignant tumor of hematopoietic precursor cells of myeloid lineage. This study is a continuation of exploring signaling nexus which can be used for building basic molecular mechanism platform in understanding pathological course of AML. Design and Setting: In this study, the animal model of AML and data from 40 AML patients was assessed. Animal model and human study was approved by ethical review board of institutions for conducting animal and human based research and according to international applicable rules and regulations. Main Outcome Measures: Experimental models were confirmed by biochemical and histological parameters. Patients were selected after detailed clinical screening for AML. Blood serum samples were processed for further analysis. Results: AML was induced in the experimental model by injecting leukemic blood in the rats. AML developed in 13-38 days after injection. Leukemic myeloblasts presence was reported in bone marrow samples of AML animal model. Enhanced Phosphorylated ARC expression was observed in AML patients as well as in AML induced rat’s samples through western blotting. Data showed ARC over expression leads to median increase in potassium concentration; p value 0.007 and significant increase in calcium; p value 0.0001. Conclusion: An increase in the expression of calcium binding protein ARC may inhibit calcium-dependent apoptotic processes and progress toward the development of AML. In the future, further studies are required to delineate exact molecular mechanism of this nexus and identify potential therapeutic targets against AML. Funding: Quaid-i-Azam University Pakistan: Grant entitled “URF” to Iram Murtaza