Acute myeloid leukemia-associated antigens (AML antigens)

Acute myeloid leukemia (AML)-associated antigens represent a diverse group of proteins and molecules expressed on the surface or within the cytoplasm of AML blasts and leukemic stem cells (LSCs). These antigens, such as CD33, CD123, and CLL-1, serve as critical targets for modern immunotherapy and targeted molecular therapies because they are often overexpressed or mutated in malignant cells compared to their healthy counterparts. Their biological roles vary widely, ranging from cytokine receptors and adhesion molecules to transcription factors and signaling kinases that drive the uncontrolled proliferation and survival of leukemic cells. In the clinical setting, these antigens are exploited to deliver cytotoxic agents via antibody-drug conjugates or to prime the immune system through CAR-T cells and bispecific antibodies. However, a significant challenge in targeting these antigens is the potential for on-target off-tumor toxicity, as many are also expressed on normal hematopoietic stem and progenitor cells, leading to severe myelosuppression. Additionally, the high degree of clonal heterogeneity in AML often necessitates combinatorial targeting strategies to prevent antigen escape and disease relapse. Understanding the expression profile and functional relevance of these antigens is essential for the development of personalized treatment regimens and effective monitoring of minimal residual disease.

Other names

Tumor antigens on Acute Myeloblastic Leukemia cellsLeukemia-associated antigens (LAAs)AML surface markersMyeloid-associated antigensAML-specific antigens

Drugs targeting these antigens utilize various mechanisms including antibody-drug conjugation (ADC) for targeted cytotoxicity, bispecific T-cell engagers (BiTEs) to redirect immune cells, chimeric antigen receptor (CAR) T-cell therapy for cellular immunotherapy, and small molecule inhibition of oncogenic signaling (e.g., kinase inhibitors).