CD34⁺
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CD34 is a transmembrane phosphoglycoprotein
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the
cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
protocol that identifies cell surface antigens. CD34 was first described on
hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...
s independently by Civin et al. and Tindle et al. as a cell surface
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
and functions as a cell-cell adhesion factor. It may also mediate the attachment of hematopoietic
stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
to
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
extracellular matrix or directly to
stromal cell Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mu ...
s. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells; however, it is actually found on many other cell types as well.


Function

The CD34 protein is a member of a family of single-pass transmembrane
sialomucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...
proteins that show expression on early
haematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten b ...
and vascular-associated progenitor cells. However, little is known about its exact function. CD34 is also an important adhesion molecule and is required for
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s to enter
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s. It is expressed on lymph node endothelia, whereas the
L-selectin L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the ''SELL'' gene. L-selectin belongs to the selectin family of proteins, which recognize si ...
to which it binds is on the T cell. Conversely, under other circumstances CD34 has been shown to act as molecular "Teflon" and block mast cell, eosinophil and dendritic cell precursor adhesion, and to facilitate opening of vascular lumina. Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors. Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.


Tissue distribution

CD34 is expressed in hematopoietic progenitor cells and
endothelial cells The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
of blood vessels. Thus, it has been used as a marker for capillaries and blood vessels. One of the most densely vascular organs is the kidney, wherein networks of capillaries are intertwined with renal tubules. In kidney sections, these networks of capillaries have been visualized by confocal microscopy of fluorescently labelled anti-CD34 antibodies. The presence of CD34 on non-hematopoietic cells in various tissues has been linked to progenitor and adult stem cell phenotypes. It is important to mention that Long-Term Haematopoietic Stem Cells (LT-HSCs) in mice and humans are the haematopoietic cells with the greatest self-renewal capacity and were shown to be CD34+ and CD38 cell fraction within the lineage-depleted cell population (LIn). Human HSCs express the CD34 marker. Later studies have reported that low rhodamine retention identifies LT-HSCs within the LinCD34+CD38 population. CD34 is expressed in roughly 20% of murine haematopoietic stem cells, and can be stimulated and reversed.


Clinical applications

CD34+ is often used clinically to quantify the number of haemopoietic stem cells for use in haemopoietic stem cell transplantation. This is generally a useful marker for cell dosing although there is some evidence that the CD34+ quantification may not be reliable in some circumstances. CD34+ cells may be isolated from
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
samples using immunomagnetic techniques and used for CD34+ transplants, which have lower rates of
graft-versus-host disease Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which rema ...
. Antibodies are used to quantify and purify
hematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...
progenitor In genealogy, a progenitor (rarer: primogenitor; or ''Ahnherr'') is the founder (sometimes one that is legendary) of a family, line of descent, gens, clan, tribe, noble house, or ethnic group.. Ebenda''Ahnherr:''"Stammvater eines Geschlec ...
stem cells for research and for clinical bone marrow transplantation. However, counting CD34+ mononuclear cells may overestimate
myeloid Myeloid tissue, in the bone marrow sense of the word '' myeloid'' ('' myelo-'' + '' -oid''), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (''myelo-'' + '' -genous'') is any tissue ...
blasts in bone marrow smears due to hematogones (B lymphocyte precursors) and CD34+
megakaryocytes A megakaryocyte () is a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but ca ...
. Cells observed as CD34+ and CD38- are of an undifferentiated, primitive form; i.e., they are
multipotent hematopoietic stem cell Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...
s. Thus, because of their CD34+ expression, such undifferentiated cells can be sorted out. In tumors, CD34 is found in
alveolar soft part sarcoma Alveolar soft part sarcoma, abbreviated ASPS, is a very rare type of soft-tissue sarcoma, that grows slowly and whose cell of origin is unknown. ASPS arises mainly in children and young adults and can migrate (metastasize) into other parts of the ...
,
preB-ALL Precursor B-cell lymphoblastic leukemia is a form of lymphoid leukemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the blood and bone marrow. It is the most common type of acute lymphoblastic leukemia Ac ...
(positive in 75%), AML (40%),
AML-M7 Acute megakaryoblastic leukemia (AMKL) is life-threatening leukemia in which malignant megakaryoblasts proliferate abnormally and injure various tissues. Megakaryoblasts are the most immature precursor cells in a platelet-forming lineage; they mat ...
(most),
dermatofibrosarcoma protuberans Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the U ...
, gastrointestinal
stromal tumor Gastrointestinal stromal tumors (GISTs) form in the soft mesenchymal tissue of the gastrointestinal tract and form from the rapid growth of interstitial cells of Cajal (ICCs). GISTs are the most common type of tumor found in the gastrointestinal t ...
s,
giant cell fibroblastoma Giant cell fibroblastoma (GCF) is a rare type of soft-tissue tumor marked by painless nodules in the dermis (the inner layer of the two main layers of tissue that make up the skin) and subcutaneous (beneath the skin) tissue. These tumors may ...
, granulocytic sarcoma,
Kaposi’s sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses on the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...
,
liposarcoma Liposarcomas are the most common subtype of soft tissue sarcomas, accounting for at least 20% of all sarcomas in adults. Soft tissue sarcomas are rare neoplasms with over 150 different histological subtypes or forms. Liposarcomas arise from the ...
,
malignant fibrous histiocytoma Undifferentiated pleomorphic sarcoma (UPS), also termed pleomorphic myofibrosarcoma, high-grade myofibroblastic sarcoma, and high-grade myofibrosarcoma, is characterized by the World Health Organization (WHO) as a rare, poorly differentiated neopl ...
, malignant peripheral nerve sheath tumors, meningeal
hemangiopericytoma A hemangiopericytoma is a type of soft-tissue sarcoma that originates in the pericytes in the walls of capillaries. When inside the nervous system, although not strictly a meningioma tumor, it is a meningeal tumor with a special aggressive behav ...
s,
meningioma Meningioma, also known as meningeal tumor, is typically a slow-growing tumor that forms from the meninges, the membranous layers surrounding the brain and spinal cord. Symptoms depend on the location and occur as a result of the tumor pressing ...
s,
neurofibroma A neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system. In 90% of cases, they are found as stand-alone tumors (solitary neurofibroma, solitary nerve sheath tumor or sporadic neurofibroma), while the remainder are found in ...
s,
schwannoma A schwannoma (or neurilemmoma) is a usually benign nerve sheath tumor composed of Schwann cells, which normally produce the insulating myelin sheath covering peripheral nerves. Schwannomas are homogeneous tumors, consisting only of Schwann cells ...
s, and
papillary thyroid carcinoma Papillary thyroid cancer (papillary thyroid carcinoma, PTC) is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases.Chapter 20 in: 8th edition. It occurs more frequently in women and presents ...
. A negative CD34 may exclude Ewing's sarcoma/PNET, myofibrosarcoma of the breast, and
inflammatory myofibroblastic tumor Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm of the mesodermal cells that form the connective tissues which support virtually all of the organs and tissues of the body. IMT was formerly termed inflammatory pseudotumor. Currently, h ...
s of the stomach. Injection of CD34+
hematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...
stem cells has been clinically applied to treat various diseases including spinal cord injury, liver cirrhosis and peripheral vascular disease.


Interactions

CD34 has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
CRKL Crk-like protein is a protein that in humans is encoded by the CRKL gene. Function v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains. CRKL has been shown to activate the RAS and JUN kinase signaling pat ...
. It also interacts with
L-selectin L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the ''SELL'' gene. L-selectin belongs to the selectin family of proteins, which recognize si ...
, important in
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. CD34- has been related to hair follicles' melanocyte regeneration and CD34+ with neuronal regeneration.


See also

*
Cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
*
List of histologic stains that aid in diagnosis of cutaneous conditions A number of histologic stains are used in the field of dermatology that aid in the diagnosis of conditions of or affecting the human integumentary system. Footnotes See also * List of conditions associated with café au lait macules * L ...


References


Further reading

* * * * * * * * * * * * * * * * * * * * *


External links

*
Mouse CD Antigen Chart


* {{DEFAULTSORT:Cd34 Clusters of differentiation Cell adhesion molecules