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With advances in molecular medicine and precision approaches, there has been significant improvement in the treatment of acute myeloid leukemia (AML) in recent years. This reflects better understanding of molecular and metabolic pathways in leukemia cells, including BCL2 upregulation that prevents apoptosis, FLT3 tyrosine kinase activating mutations that allow uncontrolled proliferation, and IDH mutations that result in differentiation block. We performed a compressive review of important pre-clinical studies in AML that involve major molecular and metabolic pathways in AML, and we discussed standard therapeutic modalities and ongoing clinical trials for patients with AML, as well as an overall update of recent efforts in this area. Targeting these pathways has resulted in improvement in the overall survival of some groups of AML patients. Secondary AML and TP53 mutated AML remain challenging subtypes of AML with limited treatment options and represent areas of unmet research need. Ongoing work with menin inhibitors in MLL rearranged leukemia, which comprise a large portion of secondary AML cases, the development of CAR T cell products and targeting the CD47 receptor on macrophages in myeloid neoplasms including in TP53 mutated AML have provided hope for these challenging subtypes of AML.

Advances in the pharmacological management of acute myeloid leukemia in adults