Human Myeloid Inhibitory C-Lectin (hMICL): A Novel Acute Myeloid Leukemia Marker

Abstract

The Human Myeloid Inhibitory C-Lectin (hMICL) also known as Human C-type lectin-like molecule-1 (CLL-1), or C-type lectin domain family 12 member A (CLEC12A), is a type II transmembrane glycoprotein and member of the large family of C-type lectin-like receptors involved in immune regulation. The hMICL is a pan-myeloid antigen that is absent on normal uncommitted primitive CD34+ CD38- or CD34+ CD33- stem cells; which aids the discrimination between normal and leukemic stem cells, as well as introduces hMICL as a promising therapeutic target for eradication of antigen-bearing leukemic cells and the subsequent re-establishment of normal hematopoiesis through the remaining normal stem cells. In the absence of leukemia specific markers, the distinction between leukemic and normal immature cell relies on the expression of antigen combinations defining leukemia-associated IPs (LAIPs), which are absent or extremely infrequent in normal bone marrow (NBM). There is, however, evidence in the literature which has outlined that these LAIPs are very different from patient to patient and that they are not necessarily stable over the course of disease. Consequently, there is still a need for the identification of new antigens contributing to diagnostic and prognostic information, improving relapse detection, identification, and ideally eradication of leukemic stem cells (LSCs) through antibody mediated targeted therapy.