C-type lectin domain family 12 member A (CLEC12A) (CLEC12A)

C-type lectin domain family 12 member A (CLEC12A), also known as C-type lectin-like molecule 1 (CLL-1), is a type II transmembrane glycoprotein that functions as an inhibitory receptor on myeloid cells (UniProt Q5QGZ9). It contains an extracellular C-type lectin-like domain and an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) that modulates immune signaling (PMID: 33897515). In healthy individuals, CLEC12A is expressed on monocytes, dendritic cells, and granulocytes, but it is notably absent from pluripotent hematopoietic stem cells (HSCs) (PMID: 32066471). In the context of hematologic malignancies, CLEC12A is highly overexpressed on the surface of leukemic blasts and leukemic stem cells (LSCs) in the majority of acute myeloid leukemia (AML) patients (PMID: 33897515). This differential expression pattern makes it an ideal therapeutic target, as it allows for the selective eradication of malignant clones while potentially sparing the regenerative HSC population (PMID: 32066471). Therapeutic approaches currently under investigation include chimeric antigen receptor (CAR) T-cells, bispecific T-cell engagers, and antibody-drug conjugates (NCT03038230, PMID: 32066471). Clinical challenges include managing on-target off-tumor effects on mature myeloid cells, which can lead to transient myelosuppression and increased infection risk (PMID: 33897515).

Other names

C-type lectin-like molecule 1CLL-1CLL1MICLCD371C-type lectin domain family 12 member A

Targeted cell depletion via T-cell redirection, chimeric antigen receptor-mediated cytotoxicity, or antibody-dependent cellular cytotoxicity.