Therapeutic approaches targeting oncogenic proteins in myeloid leukemia: challenges and perspectives

IntroductionLeukemia is typically categorized into myeloid leukemia and lymphoblastic leukemia based on the origins of leukemic cells. Myeloid leukemia is a group of clonal malignancies characterized by the presence of increased immature myeloid cells in both the bone marrow and peripheral blood. Of note, the aberrant expression of specific proteins or the generation of fusion proteins due to chromosomal abnormalities are well established drivers in various forms of myeloid leukemia. Therefore, these oncoproteins represent promising targets for drug development.Areas coveredIn this review, we comprehensively discussed the pathogenesis of typical leukemia oncoproteins and the current landscape of small molecule drugs targeting these oncogenic proteins. Additionally, we elucidated novel strategies, including proteolysis-targeting chimeras (PROTACs), hyperthermia, and genomic editing, which specifically degrade oncogenic proteins in myeloid malignancies.Expert opinionAlthough small molecule drugs have significantly improved the prognosis of oncoprotein-driven myeloid leukemia patients, drug resistance due to the mutations in oncoproteins is still a great challenge in the clinic. New approaches such as PROTACs, hyperthermia, and genomic editing are considered promising approaches for the treatment of oncoprotein-driven leukemia, especially for drug-resistant mutants.