Molecular Signatures in Acute Myeloid Leukemia: From Diagnosis to Targeted Therapy and Drug Repositioning

Acute myeloid leukemia (AML) is a heterogeneous disease defined by the proliferation of immature myeloid progenitor cells in the bone marrow that impairs normal blood cell development and leads to bone marrow failure. AML is characterized by a variety of chromosomal abnormalities and gene mutations. These abnormalities and mutations result in marked differences in response to chemotherapy and survival. The cytogenetic and molecular genetic abnormalities associated with AML are not mutually exclusive and often co-occur in leukemic cells diagnosed with the disease. Analysis of the molecular alterations associated with chromosomal and genetic abnormalities in AML could provide a basis for treatment planning and identification of biomarkers for AML treatment. Based on increasingly available molecular genetics for precision medicine, AML is being subdivided into recurrent molecular entities. Emerging therapies include daunorubicin/cytarabine, tyrosine kinase inhibitors directed against FLT3, IDH inhibitors, Bcl-2 inhibitors, metabolic inhibitors, and demethylating drugs that form the basis for innovative multimodality therapy. AML patients will benefit from some new treatments, but more affordable options are needed. One source of potential treatments with known toxicity profiles and reasonable prices is repurposing or repositioning drugs. The development of antileukemic drugs for well-defined patient subgroups must be accompanied by research and the development of biomarkers of response.