Dr. Ahsanuddin Online: Lecture Supplementary Materials - FYI Only
Dr. Ahsanuddin Online: Lecture Supplementary Materials - FYI Only
Immature Markers:
CD34
This marker is a cell surface glycoprotein that functions as a cell–cell adhesion factor, and is used as a marker for immature cells, such as hematopoietic stem cells (HSC) and blasts of both both B- and T-lineage. B-cell blasts express CD34 on their surface at the earliest stage of development.
TdT
Terminal deoxynucleotidyl tranferase (TdT) is an intracellular and intranuclear DNA polymerase that catalyzes the template-independent addition of deoxynucleotides to the 3’-hydroxyl terminus of oligonucleotide primers. TdT is strongly expressed in lymphoid precursor cells (both T and B-cells) and usually is present on blast cells in lymphoblastic leukemia/lymphoma (aka acute lymphoblastic leukemia, ALL) with the exception of very immature subtypes of T- and B-lineage ALL.
B-cell markers:
CD19
CD19 is a pan B-cell lineage specific marker involved in B-cell receptor signaling (BCR). Its function is crucial for B-cell development and it may also have a critical role in the survival and maintenance of malignant human B lineage cells.
CD22
CD22 is another pan-B cell marker, expressed from the early stages of B cell maturation in the bone marrow. It precedes expression of CD19, and is useful in identifying B cell lineage in primitive lymphoid leukemias that express limited or no surface B-cell antigens, or show aberrant expression of other T cell and myeloid markers.
CD20
CD20 is a mature B-cell marker that is involved in their activation and regulation of their growth. This molecule also acts as a cell membrane calcium channel. It is expressed later than CD19, and may not be seen in immature B cells, such as blasts.
CD10
The CD10 antigen is expressed by normal B-cell precursor cells (also known as hematogones) found in bone marrow of healthy person. The highest levels of CD10 are visible on the earliest B-cell precursors. Following the maturation path, one can see that the CD10 expression slightly decreases on older hematogones and completely disappears on mature naïve B cells. It is re-expressed during the germinal center reaction in secondary lymphoid follicles.
BCL-6
BCL6 prevents premature activation and differentiation of germinal center B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high-affinity antibodies of different isotypes.
CD5
This antigen maps to a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Normally a T-cell marker, CD5 antigen is transiently induced on the surface of normal naïve B-cells when they are exposed to antigen. It is believed that CD5 is expressed on early activated B cells that act as antigen-presenting cells to T cells, prior to formation of the germinal center. It is also typically present on lymphoid neoplasms derived from naïve B cells, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma.
BCL-2
This antigen is an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. It is normal seen in lymphoid cells that are ‘immortal’ and non-proliferative, such as naïve and memory B cells. It is normally lost when lymphoid cells begin to proliferate, as in the germinal center. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma.
MUM1
The MUM1/IRF4 protein is overexpressed in late plasma-cell-directed stages of B-cell differentiation, as activated B cells transition from the germinal center to the post-germinal-center mantle/marginal zones. In particular, MUM1 provides a marker for the transition from CD10/BCL-6 positivity (GC B cells) to CD138 expression (immunoblasts and plasma cells).
CD138
CD138 is a member of the syndecan family of type I transmembrane proteoglycans, comprised of a core protein, and glycosylated with chondroitin and heparan sulfate (HS) moieties. In the immune system, CD138/Syndecan-1 is upregulated over 1000-fold during B-cell differentiation to antibody-producing plasma cells. However, its expression should be interpreted with caution, as CD138 is also expressed at high levels in epithelial cells and at lower levels on a variety of cell types, including endothelial cells and fibroblasts, with a diverse array of functions.
T cell markers
CD2
CD2 is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It is a pan T cell marker, expressed at all stages of T cell development.
CD3
CD3 is a protein complex and T cell co-receptor that is involved in activating both the cytotoxic T cell (CD8+ naive T cells) and T helper cells (CD4+ naive T cells). It is composed of four distinct chains. The complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with the T-cell receptor (TCR) and the CD3-zeta (ζ-chain) to generate an activation signal in T lymphocytes. The TCR, CD3-zeta, and the other CD3 molecules together constitute the TCR complex. Note that NK cells lack the extracellular chains that make up the surface antigen, as the TCR is not expressed. However, the intracellular CD3-epsilon chains are still expressed, and can be visualized with CD3 polyclonal immunostains, which detect the cytoplasmic portion of the marker. CD3 is a mature T cell marker, and is not necessarily expressed on immature T lineage cells, such as blasts.
CD4
CD4 antigen is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. These cells act as antigen presenting cells to cytotoxic and phagocytic cells, giving rise to the ‘helper’ phenotype.
CD8
CD8 antigen is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen interactions. CD8 typically binds to antigen presenting cells which express MHC I proteins. The CD8 co-receptor is predominantly expressed on the surface of cytotoxic T cells, but can also be found on natural killer cells, cortical thymocytes, and dendritic cells. The CD8 molecule is a marker for cytotoxic T cell population.
CD45
The CD45 antigen (aka leukocyte common antigen—LCA) is a glycoprotein with a heavily glycosylated extracellular domain, a transmembrane segment, and a cytoplasmic fragment with tyrosine phosphatase activity. CD45 is a regulator of T-and B-cell-receptor signaling. CD45 is expressed on all hematopoietic cells except erythroblasts, erythrocytes, and platelets, with the strongest expression on lymphocytes and neutrophils. B blasts typically have dimmer expression of CD45 than mature lymphocytes. CD45 is not expressed on the Reed-Sternberg cells of classic Hodgkin lymphoma.
BCL1/cyclin D1
The product of the CCND1 gene, cyclin D1 protein belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of cyclin-dependent kinases which contribute to the temporal coordination of each mitotic event, regulating progression through the cell cycle. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition.
LEF1
Lymphoid enhancer-binding factor-1 (LEF1) is a nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha (TCRA) enhancer and confers maximal enhancer activity. It is highly overexpressed in chronic lymphocytic leukemia (CLL), and shows a high specificity (92%) and a reasonable sensitivity (70%) for this entity.
Ki-67
Ki-67 antigen is a nuclear protein that is associated with cellular proliferation. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is particularly overexpressed in S phase. It is typically absent in resting (quiescent) cells (G0).
MYC
MYC protein is collectively derived from a family of genes that encode transcription factors and proto-oncogenes. There are three main forms are c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). In cancer, c-myc is often constitutively expressed, which leads to the increased expression of up to 15% of all genes, some of which are involved in cell proliferation. A major effect of c-myc is B cell proliferation, and gain of MYC has been associated with B cell malignancies and their increased aggressiveness, including histological transformation.
CD30
CD30 is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker. This receptor is expressed by activated, but not by resting, T and B cells. It mediates the signal transduction that leads to the activation of NF-kappaB. CD30 is strongly expressed on anaplastic large cell lymphoma (ALCL), as well as the Reed-Sternberg cells (and Hodgkin variant cells) of classic Hodgkin lymphoma (CHL). CD30 is the target of the FDA-approved therapeutic agent brentuximab, used in salvage therapy for treatment resistant cases of both CHL and ALCL.
CD15
CD15 is expressed by monocytes and granulocytes and is involved in carbohydrate interactions and phagocytosis. CD15 is expressed at highest levels on mature granulocytes. CD15 is variably expressed on Reed-Sternberg cells of classic Hodgkin lymphoma.
CD56
Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia, skeletal muscle, and the hematopoietic system. During hematopoiesis, CD56 is the prototypic marker of NK cells, also present on subset of CD4+ T cells and CD8+ T cells. NCAM has been implicated as having a role in cell–cell adhesion, neurite outgrowth, synaptic plasticity, and learning and memory.
MYD88
Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene. The MyD88 protein acts as an adapter, connecting proteins that receive signals from outside the cell to the proteins that relay signals inside the cell. Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in activated B cell (ABC) subtype of diffuse large B-cell lymphoma and lymphoplasmacytic lymphoma.
CD123
CD123 molecule, also known as the interleukin-3 receptor alpha chain (IL-3Rα) is normally expressed by plasmacytoid dendritic cells. Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialized in secreting high levels of type I interferons. pDCs play a crucial role in antiviral immunity and have been implicated in the initiation and development of many autoimmune and inflammatory diseases.
CD117
Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, aka CD117 or mast/stem cell growth factor receptor (SCFR). Signaling through KIT plays a role in cell survival, proliferation, and differentiation. In the hematopoietic system, activating mutations in this gene are associated with mast cell disease and acute myeloid leukemia. These activating mutations are often vulnerable to suppression by tyrosine kinase inhibitors, which are particular important in the treatment of mast cell disease.
CD38
CD38 is type II membrane glycoprotein that plays a role in cell adhesion, migration, and signal transduction. CD38 is strongly and consistently expressed by B-cell precursors and plasma cells, and in CLL, it may be used as a surrogate marker for lymphoma cells which have not yet undergone somatic hypermutation. This marker has been largely replaced by direct detection of somatic hypermutation, via molecular techniques.
CD13
A marker normally associated with myeloid cell lineages, involved in the alteration of target cell specificity and acting to activate or inhibit bioactive proteins. CD13 also controls the chemotactic response of neutrophils to IL-8 and is involved in tumor migration as it supports cell adhesion.
Cytoplasmic IgM (cy-IgM)
As a component of normal B-cell receptors, cytoplasmic expression of this heavy immunoglobulin chain receptor starts at the stage of late pre-B-I cell and is upregulated along further maturation of B-cells in BM.
CD33
CD33 is a transmembrane sialic acid binding immunoglobulin-type lectin (SIGLEC) receptor which is involved in negative selection of human self-regenerating stem cells. Other known functions of CD33 include apoptosis induction and cytokine secretion modulation. IN the hematopoietic system, CD33 is typically associated with myeloid differentiation.
© Copyright. All rights reserved.
We need your consent to load the translations
We use a third-party service to translate the website content that may collect data about your activity. Please review the details in the privacy policy and accept the service to view the translations.