CD33 is a member of the sialic acid-binding immunoglobulin-like lectins, a discrete subset of the immunoglobulin (Ig) superfamily molecules. CD33 is a 67 kDa glycosylated transmembrane protein. It is characterized by an amino-terminal V-set Ig-like domain that mediates sialic acid-binding and a C2-set Ig-like domain in the extracellular portion. CD33 contains two tyrosine residues on its cytoplasmic tail, each of which is followed by hydrophobic residues similar to the immunoreceptor tyrosine-based inhibitory motif (ITIM) seen in many inhibitory receptors. CD33 has endocytic properties when bound by bivalent antibodies that result in the internalization of the antigen/antibody complex. These domains are phosphorylated by SRC family kinases. CD33, or myeloid differentiation antigen, is expressed only on hematopoietic cells. It is expressed on most myeloid and monocytic leukemia cells in addition to committed myelomonocytic and erythroid progenitor cells. It is not seen on the earliest pluripotent stem cells, mature granulocytes, lymphoid cells, or nonhematopoietic cells.
Fig.1 Structure and signaling pathway of CD33.(Laing, 2017)
In healthy individuals, CD33 is normally expressed on the myeloid lineage at the early stages of myeloid differentiation. As myeloid maturation occurs, CD33 expression is downregulated. CD33 is highly expressed on blast cells in 85-90% of patients presenting with acute myeloid leukemia (AML). In addition to its expression in AML, CD33 is found not only on abnormal cells in other myeloid neoplasms but also on subsets of B-cell and T-cell acute lymphoblastic leukemia (ALL)/lymphoblastic lymphomas, perhaps consistent with its occasional expression on normal non-myeloid cells. The function of CD33 in normal and AML cells remains largely unknown. There is increasing evidence that it negatively regulates inflammatory reaction and immune responses through inhibiting effects on tyrosine kinase-driven signaling pathways.
Many studies over several decades have proposed using CD33 as a target for cancer therapeutic drugs, and specifically targeting AML by CD33-specific antibodies. However, most efforts have been unsuccessful, because CD33 is expressed on normal hematopoietic cells, causing the unexpected cell death of normal cells by those CD33-related antibodies conjugated with anticancer drugs.
Due to the high frequency of CD33 expression on AML blasts, the absent or lower CD33 expression on normal hematopoietic stem cells and its endocytic properties, CD33 has been of interest as a therapeutic target. Creative Biolabs provides a set of CD33 assay portfolio services, including CD33 immunohistochemistry and immunofluorescence, quantitation of CD33 expression, cellular uptake assay, cytotoxicity assay, cell proliferation assay, cell apoptosis assay, ELISA, flow cytometry, and so on.
Creative Biolabs is dedicated to providing and developing a series of tumor marker assay services for our customers. With the help of high technology and an experienced scientist team, Creative Biolabs strives to meet our customers’ challenging requirements. We provide scientific consultancy and customized project management throughout your entire study. Please feel free to contact us for more information.
Reference
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