Leukemia-associated antigen (LAA) (LAA)

Leukemia-associated antigens (LAAs) are a heterogeneous group of proteins and glycoproteins expressed on the surface of acute myeloid leukemia (AML) blasts and leukemic stem cells. These antigens, which include CD33, CD123, CLL-1, and FLT3, play vital roles in cell signaling, proliferation, and survival within the leukemic microenvironment (Perna et al., 2017, Cancer Cell). In AML, LAAs are utilized as therapeutic targets to facilitate the selective destruction of malignant cells while attempting to minimize damage to healthy tissues. Therapeutic modalities targeting these antigens range from monoclonal antibodies and antibody-drug conjugates to advanced cellular therapies like CAR-T cells (Lichtenegger et al., 2017, Frontiers in Oncology). For instance, Gemtuzumab ozogamicin targets CD33 to deliver a cytotoxic calicheamicin payload directly to the leukemia cells (Walter et al., 2012, Blood). Despite their utility, many LAAs are also expressed on normal myeloid progenitors, leading to significant safety concerns such as prolonged myelosuppression and cytopenias. The identification and validation of highly specific LAAs remain a primary focus of research to improve the therapeutic index of AML treatments. Monitoring the expression of these antigens also serves as a critical biomarker for patient stratification and the assessment of minimal residual disease.

Other names

AML-associated antigenMyeloid-associated antigenLeukemia-specific antigenTumor-associated antigen in AML

Antibody-drug conjugation, receptor tyrosine kinase inhibition, antibody-dependent cellular cytotoxicity (ADCC), and chimeric antigen receptor (CAR) T-cell mediated lysis (Stein et al., 2018, Blood Reviews).