Precision Medicine in Myeloid Neoplasia: Challenges and Opportunities

High-risk myeloid neoplasms encompass a group of hematologic malignancies known to cause significant cytopenias, which are accompanied by the risk of end-organ damage. They tend to have an aggressive clinical course and limit life expectancy in the absence of effective treatments. The adoption of precision medicine approaches has been limited by substantive diversity in somatic mutations, limited fraction of patients with targetable genetic lesions, and the prolonged turnaround times of pertinent genetic tests. Efforts to incorporate targeted agents into first-line treatment, rapidly determine pre-treatment molecular or cytogenetic aberrations, and evaluate functional vulnerabilities ex vivo hold promise for advancing the use of precision medicine in these malignancies. Given the relative accessibility of malignant cells from blood and bone marrow, precision medicine strategies hold great potential to shape future standard-of-care approaches to patients with high-risk myeloid malignancies. This review aims to summarize the development of the targeted therapies currently available to treat these blood cancers, most notably acute myeloid leukemia, and also evaluate future opportunities and challenges related to the integration of personalized approaches.