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

Abstract

Introduction: Leukemia is typically categorized into myeloid leukemia and lymphoblastic leukemia based on the origins of leukemic cell. Myeloid leukemia is a group of clonal malignancies characterized by the presence of increased immature myeloid cells in both 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 covered: In this review, we comprehensively discussed the pathogenesis of typical leukemia oncoproteins and 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 opinion: Although 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 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.