CD33 Marker

CD33 is a transmembrane glycoprotein belonging to the sialic acid-binding immunoglobulin-like lectin (Siglec) family. Siglecs are a group of cell surface receptors involved in cell-cell interactions and immune responses. CD33 is expressed on various myeloid cells, including early hematopoietic precursors, mature neutrophils, and a subset of monocytes/macrophages. It binds to CD3 to help T-cells recognize antigens bound to class II major histocompatibility molecules displayed by antigen-presenting cells (APCs). Other ligands for CD33 include CD62L and CD64. Generally localized within the mitochondria, CD33 relocates to the cell membrane under increased cellular stress due to hypoxia or nutrient deprivation.

CD33 plays a role in various immune functions by enabling T-cell killing of neutrophil precursors via phagocytosis, enhancing neutrophil adhesion to endothelium at inflammatory sites, and regulating dendritic cell maturation for T helper 2 responses against extracellular pathogens and CD4 responses against allergens. CD33 antibodies have been shown to induce apoptosis in CD33-expressing cells. Originally, it was thought that CD33-mediated signal transduction occurred through the immunoreceptor tyrosine-based activation motif (ITAM) via ITAM phosphorylation by Lyn or Syk. However, it is now known that CD33 does not activate allogeneic T-cells when co-engaged with class II MHC molecules. Instead, CD33 functions as an ion channel, allowing ions such as potassium to flow in and out of cells through the protein.

CD33 has been extensively studied as a biomarker for cancer, particularly in myeloproliferative disorders like chronic myeloid leukemia (CML). CD33 is used to study CD3 T-cells, which can be altered during certain cancers.

CD33 is a frequently used marker for the diagnosis and monitoring of acute myeloid leukemia (AML). CD33 is expressed on the surface of myeloid cells, including the leukemic blasts that are characteristic of AML. Detection of CD33 on these cells is therefore useful in distinguishing AML from other types of leukemia and in monitoring disease progression. Additionally, CD33 is the target of the therapeutic monoclonal antibody gemtuzumab ozogamicin, which is used to treat some patients with AML. The binding of gemtuzumab ozogamicin to CD33 on leukemic blasts triggers cell death, making this therapeutic approach effective for certain AML cases.

CD33 is currently being investigated as a treatment for several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). In these diseases, CD33 may play a role in the immune system's response to neural tissue damage. In Alzheimer's disease, CD33 has been implicated in the formation of amyloid plaques and the subsequent inflammation and damage to neurons. In Parkinson's disease, CD33 has been found to be upregulated in microglia, which are immune cells in the brain that play a role in neuroinflammation. CD33 inhibition is being studied as a potential therapeutic strategy to reduce inflammation and protect neurons in these diseases.

CD33-based therapeutics hold significant promise for the treatment of cancer and other diseases. One promising approach involves using CD3 antagonists to increase CD3 T-cell cytotoxicity and reduce CD33 cells. In preclinical trials, CD33-binding antagonists have been shown to bind CD33 on CD3 cells, prevent CD33 from functioning, and thereby inhibit CD3 T-cell apoptosis while increasing their ability to kill tumors. This approach has been effective in killing tumors in mouse models of leukemia, and further research is underway to explore its potential in treating other types of cancer.

CD33 is also being investigated for potential therapeutic applications beyond cancer. For example, it has been studied as a potential therapeutic target for sickle cell anemia. CD33 inhibits vaso-occlusive crisis and is associated with increased blood flow and oxygen concentration, which alleviates sickle cell symptoms such as pain and organ damage due to hypoxia. Cell signaling inhibitors are being developed to bind CD33 directly, interrupting its ion channel activity without affecting other functions associated with CD33. Although these drugs are still in early trials, they have shown promise as potential treatments for chronic lymphocytic leukemia.

CD33 has been used as a target for cancer nanotherapies, with CD33-binding nanoparticles being developed to accumulate in tumors and deliver a chemotherapeutic payload directly to tumor cells. This approach has the potential to improve chemotherapy efficacy and reduce side effects by targeting only cancer cells.

CD33 is a commonly used marker for flow cytometry analysis of myeloid cells. Flow cytometry is a technique that allows for the analysis of individual cells based on their physical and chemical properties, including surface markers like CD33. By labeling cells with fluorescently labeled antibodies specific to CD33, it is possible to detect and analyze CD33 expression levels on individual cells using flow cytometry. This analysis is useful in a wide range of applications, including the identification and classification of leukemias, monitoring of minimal residual disease, and characterization of immune cell populations in disease states. The use of CD33 as a marker in flow cytometry has greatly advanced our understanding of myeloid cell development, function, and disease.