C-type lectin domain family 12 member A is a protein that in humans is encoded by the CLEC12Agene. This gene encodes a member of the C-type lectin/C-type lectin-like domain superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively splicedtranscript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. CLEC12A, also known as MICL, is inhibitory C-type lectin-like receptor. It contains ITIM motif in cytoplasmic tail that can associate with signalling phosphatases SHP-1 and SHP-2. There are two types, human and murine. Human MICL is expressed as a monomer primarily on myeloid cells, including granulocytes, monocytes, macrophages and dendritic cells. Murine MICL is expressed as dimer on granulocytes, monocytes but also on B lymfocytes and can be also found on NK cells surface in bone marrow.
Use in therapy
In the immunotherapy of acute myeloid leukemia, CLL-1 becomes one of the target due to its high expression in AML cells while being absent in normal hematopoietic stem cells. CLL-1 is also expressed on the surface of leukemic stem cells, which possesses the ability to indefinitely self-renew, produce plenty of leukemic cells and are associated with leukemia relapses. Scientists are working on various therapeutic approaches using CLL-1 as a target for AML. One of them is development of bispecific antibodies such as CD3/CLL-1 antibody. It can recruit unstimulated primary T cells in patients against cancer cells with CLL-1 on surface. Other way is development of CAR T cells specific for CLL-1 antigen. This principle showed efficient and specific anti-leukemia activity to AML cell lines from AML patients, as well as in mouse model.
