Acute myeloid leukemia cell surface antigens (Category) (AML cell surface antigens)

Acute myeloid leukemia cell surface antigens represent a diverse collection of membrane-associated proteins that are differentially expressed on malignant myeloid cells compared to normal hematopoietic cells. These antigens span multiple molecular classes including cytokine receptors, adhesion molecules, C-type lectins, and unexpectedly, RNA-binding proteins that localize to the cell surface. The expression landscape of these antigens is highly heterogeneous, varying across AML genetic subtypes and differentiation stages. Modern single-cell RNA sequencing combined with mass spectrometry-based surfaceome profiling has revealed that AML cells at different maturation stages express distinct surface antigen profiles[1][2]. This complexity has been a major obstacle to developing effective antibody-based immunotherapies for AML, in contrast to the success seen in other hematological malignancies. Recent advances have identified several categories of therapeutically relevant surface antigens. Pan-AML markers like CD33 and CD123 are expressed across multiple AML subtypes but may also be present on normal myeloid progenitors. Leukemic stem cell-selective markers such as CLL-1, CD96, and TIM3 show enrichment on the CD34+CD38- LSC population compared to normal HSCs, though expression is often incomplete within the LSC compartment[5]. A particularly promising recent discovery is cell surface nucleophosmin (csNPM1), which forms organized nanodomains with glycosylated RNAs and other RNA-binding proteins on cancer cell surfaces. csNPM1 is expressed in a mutation-agnostic manner on primary AML blasts and leukemic stem cells but not on normal hematopoietic stem cells, making it an attractive therapeutic target[3]. Subtype-specific markers have also been identified, such as those enriched in KMT2A-rearranged AML, where surfaceome analysis revealed antigens expressed homogeneously on >90% of blast cells in affected patients[2]. The identification of 60 genes significantly overexpressed in immature AML HSC-like cells compared to normal HSCs, with 39 confirmed at the protein level and 23 nearly universally expressed across specimens, provides a rich landscape for therapeutic development[1]. The therapeutic strategy for targeting these antigens is evolving beyond traditional antibody-drug conjugates to include CAR-T cell therapies, bispecific antibodies, and mRNA vaccines. Patient stratification based on immune profiling has identified distinct immune subtypes (such as immune-hot immunosuppressive vs immune-cold phenotypes) that may determine optimal candidates for vaccination strategies[4].

Other names

AML surface markersAML cell surface markersleukemic cell surface antigensAML surfaceome antigens

Antibody-dependent cellular cytotoxicity (ADCC); Complement-dependent cytotoxicity (CDC); Direct cellular cytotoxicity through drug conjugation; CAR-T cell targeting; Immune checkpoint modulation