Acute myeloid leukemia (AML) is the most common acute leukemia in adults characterized by a clonal proliferation of myeloid precursors with a reduced capacity to differentiate into more mature cellular elements resulting in pancytopenia. Current treatment options include induction chemotherapy followed by consolidation and hematopoietic stem cell transplantation (HSCT). DNA hypomethylating agents such as decytabine have been used to treat AML, especially in older patients. The drug has shown significant clinical benefit in a recent Phase III trial in older patients demonstrating the proof of concept of inhibiting DNA methylation as a therapeutic strategy in AML. We have discovered a novel synthetic small molecule, named XB05 that has potent activity against myeloid leukemia cell lines. Its precise molecular mechanism is not yet fully understood; however, we believe that it induces leukemia cell death through multiple mechanisms, including reactivation of tumor suppressor genes via inhibition of DNA methylation. In this study, mechanistic studies were performed with this novel agent in previously established leukemia cell lines.
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