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Cyclic Amp Efflux Inhibition As A Potential Therapeutic Target For Acute Leukemia: Small Molecule Discovery And Validation, Dominique R. Perez

Biomedical Sciences ETDs

Evasion of apoptosis and resistance to chemotherapy are major therapeutic challenges for acute leukemias. Presumably as a means to promote cell survival, multiple elements of the cyclic AMP (cAMP) pathway are aberrantly regulated in acute leukemias. Furthermore, increased intracellular cAMP (icAMP) is known to induce apoptosis. Therefore, modulation of icAMP has long been a target in leukemias. The central hypothesis of this dissertation is that malignant cells produce and remove excess intracellular cAMP to evade apoptosis and promote survival. Consequently, inhibition of cAMP efflux could selectively trigger leukemia cell death. We designed a novel assay to assess icAMP efflux from …