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{{Infobox_gene}}
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
'''CD34''' is a transmembrane phosphoglycoprotein [[protein]] encoded by the CD34 gene in humans, mice, rats and other species.<ref>{{cite web | title = Entrez Gene: CD34 CD34 molecule| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=947| accessdate = }}</ref><ref name="pmid1370171">{{cite journal | vauthors = Simmons DL, Satterthwaite AB, Tenen DG, Seed B | title = Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells | journal = Journal of Immunology | volume = 148 | issue = 1 | pages = 267–71 | date = Jan 1992 | pmid = 1370171 | url = http://www.jimmunol.org/cgi/content/abstract/148/1/267 }}</ref><ref name="pmid1374051">{{cite journal | vauthors = Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG | title = Structure of the gene encoding CD34, a human hematopoietic stem cell antigen | journal = Genomics | volume = 12 | issue = 4 | pages = 788–94 | date = Apr 1992 | pmid = 1374051 | doi = 10.1016/0888-7543(92)90310-O }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = CD34 molecule
| HGNCid = 1662
| Symbol = CD34
| AltSymbols =;
| OMIM = 142230
| ECnumber = 
| Homologene = 1343
| MGIid = 88329
| GeneAtlas_image1 = PBB_GE_CD34_209543_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0030246 |text = carbohydrate binding}}  
| Component = {{GNF_GO|id=GO:0009897 |text = external side of plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0007155 |text = cell adhesion}} {{GNF_GO|id=GO:0016337 |text = cell-cell adhesion}} {{GNF_GO|id=GO:0050900 |text = leukocyte migration}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 947
    | Hs_Ensembl = ENSG00000174059
    | Hs_RefseqProtein = NP_001020280
    | Hs_RefseqmRNA = NM_001025109
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 206116942
    | Hs_GenLoc_end = 206151370
    | Hs_Uniprot = P28906
    | Mm_EntrezGene = 12490
    | Mm_Ensembl = ENSMUSG00000016494
    | Mm_RefseqmRNA = NM_133654
    | Mm_RefseqProtein = NP_598415
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 196639610
    | Mm_GenLoc_end = 196662005
    | Mm_Uniprot = Q3TJP6
  }}
}}


'''CD34 molecule''' is a [[cluster of differentiation]] [[molecule]] present on certain cells within the human body. It is a cell surface [[glycoprotein]] and functions as a cell-cell [[adhesion]] [[factor]]. It may also mediate the attachment of [[stem cells]] to [[bone marrow]] extracellular matrix or directly to [[stroma|stromal cells]]. '''CD34''' is the human [[gene]] encoding it.<ref>{{cite web | title = Entrez Gene: CD34 CD34 molecule| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=947| accessdate = }}</ref>
CD34 derives its name from the [[cluster of differentiation]] protocol that identifies cell surface antigens. CD34 was first described on [[hematopoietic stem cell]]s independently by Civin et al. and Tindle et al.<ref>{{cite journal |vauthors=Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH |title=Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells |journal=Journal of Immunology |volume=133 |issue=1 |pages=157–65 |year=1984 |pmid=6586833 |doi= |url=}}</ref><ref>{{Cite journal|last=Tindle RW. Nichols R. Chan L. Campana D. Birnie GD.|first=|date=1985|title=A novel monoclonal antibody BI-3C5 recognises myeloblasts and non-B, non-T lymphoblasts in acute leukaemia and CGL blast crises, and react with immature cells in normal bone marrow|url=|journal=Leukemia Research |volume=9 |pages=1–9|doi=10.1016/0145-2126(85)90016-5|pmid=|access-date=}}</ref><ref>{{Cite journal|last=Tindle RW. Katz F. Martin H. Watt D. Catovsky D. Janossy G. Greaves M.|first=|date=1987|title=BI-3C5 (CD34) defines multipotential and lineage restricted progenitor cells and their leukaemic counterparts .|url=|journal=In 'Leucocyte typing 111: White cell differentiation antigens. Oxford University Press, 654-655|doi=|pmid=|access-date=}}</ref><ref>{{Cite journal|last=Loken M. Shah V. Civin CI..|first=|date=1987|title=Characterization of myeloid antigens on human bone marrow using multicolour immunofluorescence|url=|journal=In: McMichael, Leucocyte Typing III:White cell differentiation antigens.Oxford University Press 630-635|doi=|pmid=|access-date=}}</ref> as a cell surface [[glycoprotein]] and functions as a [[Cell adhesion|cell-cell adhesion]] factor. It may also mediate the attachment of hematopoietic [[stem cells]] to [[bone marrow]] extracellular matrix or directly to [[stromal cell]]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.<ref name=":0" />


Cells expressing CD34 (CD34+ cell) are normally found in the [[umbilical cord]] and [[bone marrow]] as hematopoeitic cells, [[endothelial progenitor cell|endothelial progenitor cells]], [[endothelial cell]]s of blood vessels but not [[lymphatics]] (except pleural lymphatics), [[mast cells]], a sub-population  [[dendritic cell]]s (which are [[factor XIII]]a negative) in the interstitium and around the [[adnexa]] of [[dermis]] of skin, as well as cells in soft tissue tumors like [[dermatofibrosarcoma protuberans|DFSP]], [[Gastrointestinal_stromal_tumor|GIST]], [[Malignant_peripheral_nerve_sheath_tumor|PNST]]s etc.
== Function ==


==Clinical applications==
The CD34 protein is a member of a family of single-pass transmembrane [[mucin|sialomucin]] proteins that show expression on early [[hematopoietic]] and vascular-associated tissue.<ref name="pmid18987355">{{cite journal | vauthors = Nielsen JS, McNagny KM | title = Novel functions of the CD34 family | journal = Journal of Cell Science | volume = 121 | issue = Pt 22 | pages = 3683–92 | date = Nov 2008 | pmid = 18987355 | pmc =  | doi = 10.1242/jcs.037507 }}</ref> However, little is known about its exact function.<ref name="pmid16720896">{{cite journal | vauthors = Furness SG, McNagny K | title = Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis | journal = Immunologic Research | volume = 34 | issue = 1 | pages = 13–32 | year = 2006 | pmid = 16720896 | doi = 10.1385/IR:34:1:13 }}</ref>
CD34+ cells may be isolated from [[blood]] samples using [[Magnetic-activated cell sorting|immunomagnetic]] or [[Flow cytometry|immunofluorescent]] methods.  


Antibodies are used to quantify and purify [[hematopoietic]] [[progenitor]] stem cells for research and for clinical bone marrow transplantation. However, counting CD34+ mononuclear cells may overestimate [[myeloid]] blasts in bone marrow smears due to [[hematogones]] and CD34+ [[megakaryocytes]].
CD34 is also an important adhesion molecule and is required for [[T cell]]s to enter [[lymph node]]s. It is expressed on lymph node [[endothelium|endothelia]], whereas the [[L-selectin]] to which it binds is on the T cell.<ref name="pmid9466573">{{cite journal | vauthors = Berg EL, Mullowney AT, Andrew DP, Goldberg JE, Butcher EC | title = Complexity and differential expression of carbohydrate epitopes associated with L-selectin recognition of high endothelial venules | journal = The American Journal of Pathology | volume = 152 | issue = 2 | pages = 469–77 | date = Feb 1998 | pmid = 9466573 | pmc = 1857953 | doi =  }}</ref><ref name="pmid17459027">{{cite journal | vauthors = Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J | title = Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis | journal = The American Journal of Gastroenterology | volume = 102 | issue = 7 | pages = 1499–509 | date = Jul 2007 | pmid = 17459027 | doi = 10.1111/j.1572-0241.2007.01189.x }}</ref>  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.<ref name="pmid15664158">{{cite journal | vauthors = Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM | title = CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution | journal = Immunity | volume = 22 | issue = 1 | pages = 43–57 | date = Jan 2005 | pmid = 15664158 | pmc =  | doi = 10.1016/j.immuni.2004.11.014 }}</ref><ref name="pmid19853564">{{cite journal | vauthors = Strilić B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E | title = The molecular basis of vascular lumen formation in the developing mouse aorta | journal = Developmental Cell | volume = 17 | issue = 4 | pages = 505–15 | date = Oct 2009 | pmid = 19853564 | pmc =  | doi = 10.1016/j.devcel.2009.08.011 }}</ref> Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors.<ref name="pmid17557898">{{cite journal | vauthors = Blanchet MR, Maltby S, Haddon DJ, Merkens H, Zbytnuik L, McNagny KM | title = CD34 facilitates the development of allergic asthma | journal = Blood | volume = 110 | issue = 6 | pages = 2005–12 | date = Sep 2007 | pmid = 17557898 | pmc =  | doi = 10.1182/blood-2006-12-062448 | url = http://www.bloodjournal.org/content/110/6/2005.long?sso-checked=true }}</ref><ref name="pmid21642249">{{cite journal | vauthors = Blanchet MR, Bennett JL, Gold MJ, Levantini E, Tenen DG, Girard M, Cormier Y, McNagny KM | title = CD34 is required for dendritic cell trafficking and pathology in murine hypersensitivity pneumonitis | journal = American Journal of Respiratory and Critical Care Medicine | volume = 184 | issue = 6 | pages = 687–98 | date = Sep 2011 | pmid = 21642249 | pmc = 3208601 | doi = 10.1164/rccm.201011-1764OC }}</ref>  Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.<ref name="pmid18987355"/><ref name="pmid17557898" />


Cells observed as CD34+ and CD38- are of an [[differentiation|undifferentiated]], primitive form; i.e. they are [[pluripotential hemopoietic stem cell]]s. Thus, because of their CD34+ expression, such undifferentiated cells can be sorted out.
== Tissue distribution ==


In tumors, CD34 is found in alveolar soft part sarcoma, preB-ALL (positive in 75%), AML (40%), AML-M7 (most), dermatofibrosarcoma protuberans, gastrointestinal stromal tumors, giant cell fibroblastoma, granulocytic sarcoma, Kaposi’s sarcoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumors, mengingeal hemangiopericytomas, meningiomas, neurofibromas, schwannomas, and papillary thyroid carcinoma.
Cells expressing CD34 (CD34<sup>+</sup> cell) are normally found in the [[umbilical cord]] and [[bone marrow]] as hematopoietic cells, or in [[mesenchymal stem cell]]s, [[endothelial progenitor cell]]s, [[endothelial cell]]s of blood vessels but not [[lymphatics]] (except pleural lymphatics), [[mast cells]], a sub-population of [[dendritic cell]]s (which are [[factor XIII]]a-negative) in the interstitium and around the [[Skin appendage|adnexa]] of [[dermis]] of skin, as well as cells in soft tissue tumors like [[dermatofibrosarcoma protuberans|DFSP]], [[Gastrointestinal stromal tumor|GIST]], [[Solitary fibrous tumour|SFT]], [[Hemangiopericytoma|HPC]], and to some degree in [[Malignant peripheral nerve sheath tumor|MPNST]]s, etc. The presence of CD34 on non-hematopoietic cells in various tissues has been linked to progenitor and adult stem cell phenotypes.<ref name=":0">{{cite journal | vauthors = Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A | title = Concise review: evidence for CD34 as a common marker for diverse progenitors | journal = Stem Cells | volume = 32 | issue = 6 | pages = 1380–9 | date = Jun 2014 | pmid = 24497003 | pmc = 4260088 | doi = 10.1002/stem.1661 }}</ref>


A negative CD34 may exclude Ewing's sarcoma/PNET, myofibrosarcoma of the breast, and inflammatory myofibroblastic tumors of the stomach.
It is important to mention that Long-Term Hematopoietic Stem Cells (LT-HSCs) in mice and humans are the hematopoietic cells with the greatest self-renewal capacity.{{citation needed|date=January 2016}} Human HSCs express the CD34 marker.{{citation needed|date=January 2016}}


==References==
CD34 is expressed in roughly 20% of murine hematopoietic stem cells,<ref>{{cite journal | vauthors = Ogawa M, Tajima F, Ito T, Sato T, Laver JH, Deguchi T | title = CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations | journal = Annals of the New York Academy of Sciences | volume = 938 | issue = | pages = 139–45 | date = Jun 2001 | pmid = 11458501 | doi = 10.1111/j.1749-6632.2001.tb03583.x | bibcode = 2001NYASA.938..139O }}</ref> and can be stimulated and reversed.<ref>{{cite journal | vauthors = Tajima F, Sato T, Laver JH, Ogawa M | title = CD34 expression by murine hematopoietic stem cells mobilized by granulocyte colony-stimulating factor | journal = Blood | volume = 96 | issue = 5 | pages = 1989–93 | date = Sep 2000 | pmid = 10961905 | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=10961905 }}</ref>
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Simmons DL, Satterthwaite AB, Tenen DG, Seed B |title=Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells. |journal=J. Immunol. |volume=148 |issue= 1 |pages= 267-71 |year= 1992 |pmid= 1370171 |doi=  }}
*{{cite journal  | author=Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG |title=Structure of the gene encoding CD34, a human hematopoietic stem cell antigen. |journal=Genomics |volume=12 |issue= 4 |pages= 788-94 |year= 1992 |pmid= 1374051 |doi=  }}
*{{cite journal | author=Fina L, Molgaard HV, Robertson D, ''et al.'' |title=Expression of the CD34 gene in vascular endothelial cells. |journal=Blood |volume=75 |issue= 12 |pages= 2417-26 |year= 1990 |pmid= 1693532 |doi=  }}
*{{cite journal  | author=Fackler MJ, Civin CI, Sutherland DR, ''et al.'' |title=Activated protein kinase C directly phosphorylates the CD34 antigen on hematopoietic cells. |journal=J. Biol. Chem. |volume=265 |issue= 19 |pages= 11056-61 |year= 1990 |pmid= 1694174 |doi=  }}
*{{cite journal  | author=Sutherland DR, Watt SM, Dowden G, ''et al.'' |title=Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34. |journal=Leukemia |volume=2 |issue= 12 |pages= 793-803 |year= 1989 |pmid= 2462139 |doi= }}
*{{cite journal  | author=Nakamura Y, Komano H, Nakauchi H |title=Two alternative forms of cDNA encoding CD34. |journal=Exp. Hematol. |volume=21 |issue= 2 |pages= 236-42 |year= 1993 |pmid= 7678811 |doi=  }}
*{{cite journal  | author=Huyhn A, Dommergues M, Izac B, ''et al.'' |title=Characterization of hematopoietic progenitors from human yolk sacs and embryos. |journal=Blood |volume=86 |issue= 12 |pages= 4474-85 |year= 1996 |pmid= 8541536 |doi=  }}
*{{cite journal  | author=Tavian M, Coulombel L, Luton D, ''et al.'' |title=Aorta-associated CD34+ hematopoietic cells in the early human embryo. |journal=Blood |volume=87 |issue= 1 |pages= 67-72 |year= 1996 |pmid= 8547678 |doi=  }}
*{{cite journal  | author=Hillier LD, Lennon G, Becker M, ''et al.'' |title=Generation and analysis of 280,000 human expressed sequence tags. |journal=Genome Res. |volume=6 |issue= 9 |pages= 807-28 |year= 1997 |pmid= 8889549 |doi=  }}
*{{cite journal  | author=Uchida N, Yang Z, Combs J, ''et al.'' |title=The characterization, molecular cloning, and expression of a novel hematopoietic cell antigen from CD34+ human bone marrow cells. |journal=Blood |volume=89 |issue= 8 |pages= 2706-16 |year= 1997 |pmid= 9108388 |doi=  }}
*{{cite journal | author=Ruiz ME, Cicala C, Arthos J, ''et al.'' |title=Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection by HIV. |journal=J. Immunol. |volume=161 |issue= 8 |pages= 4169-76 |year= 1998 |pmid= 9780190 |doi=  }}
*{{cite journal  | author=Kees UR, Ford J |title=Synergistic action of stem-cell factor and interleukin-7 in a human immature T-cell line. |journal=Immunology |volume=96 |issue= 2 |pages= 202-6 |year= 1999 |pmid= 10233696 |doi=  }}
*{{cite journal  | author=Bistrup A, Bhakta S, Lee JK, ''et al.'' |title=Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin. |journal=J. Cell Biol. |volume=145 |issue= 4 |pages= 899-910 |year= 1999 |pmid= 10330415 |doi=  }}
*{{cite journal  | author=Lataillade JJ, Clay D, Dupuy C, ''et al.'' |title=Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival. |journal=Blood |volume=95 |issue= 3 |pages= 756-68 |year= 2000 |pmid= 10648383 |doi=  }}
*{{cite journal  | author=Felschow DM, McVeigh ML, Hoehn GT, ''et al.'' |title=The adapter protein CrkL associates with CD34. |journal=Blood |volume=97 |issue= 12 |pages= 3768-75 |year= 2001 |pmid= 11389015 |doi=  }}
*{{cite journal  | author=Dobo I, Robillard N, Pineau D, ''et al.'' |title=Use of pathology-specific peripheral blood CD34 thresholds to predict leukapheresis CD34 content with optimal accuracy: a bicentric analysis of 299 leukaphereses. |journal=Ann. Hematol. |volume=80 |issue= 11 |pages= 639-46 |year= 2001 |pmid= 11757722 |doi=  }}
*{{cite journal  | author=Hogan CJ, Shpall EJ, Keller G |title=Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 1 |pages= 413-8 |year= 2002 |pmid= 11782553 |doi= 10.1073/pnas.012336799 }}
*{{cite journal  | author=Krauter J, Hartl M, Hambach L, ''et al.'' |title=Receptor-mediated endocytosis of CD34 on hematopoietic cells after stimulation with the monoclonal antibody anti-HPCA-1. |journal=J. Hematother. Stem Cell Res. |volume=10 |issue= 6 |pages= 863-71 |year= 2003 |pmid= 11798512 |doi= 10.1089/152581601317210953 }}
*{{cite journal  | author=Okuno Y, Iwasaki H, Huettner CS, ''et al.'' |title=Differential regulation of the human and murine CD34 genes in hematopoietic stem cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 9 |pages= 6246-51 |year= 2002 |pmid= 11983914 |doi= 10.1073/pnas.092027799 }}
*{{cite journal  | author=Hotfilder M, Röttgers S, Rosemann A, ''et al.'' |title=Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal. |journal=Blood |volume=100 |issue= 2 |pages= 640-6 |year= 2002 |pmid= 12091359 |doi=  }}
}}
{{refend}}


== Clinical applications ==


CD34+ cells may be isolated from [[blood]] samples using [[Magnetic-activated cell sorting|immunomagnetic]] or [[Flow cytometry|immunofluorescent]] methods.
Antibodies are used to quantify and purify [[hematopoietic]] [[progenitor]] stem cells for research and for clinical bone marrow transplantation. However, counting CD34+ mononuclear cells may overestimate [[myeloid]] blasts in bone marrow smears due to [[hematogones]] (B lymphocyte precursors) and CD34+ [[megakaryocytes]].
Cells observed as CD34+ and CD38- are of an [[cellular differentiation|undifferentiated]], primitive form; i.e., they are [[multipotential hemopoietic stem cell]]s. Thus, because of their CD34+ expression, such undifferentiated cells can be sorted out.
In tumors, CD34 is found in [[alveolar soft part sarcoma]], [[preB-ALL]] (positive in 75%), [[acute myelogenous leukemia|AML]] (40%), [[AML-M7]] (most), [[dermatofibrosarcoma protuberans]], gastrointestinal [[stromal tumor]]s, [[giant cell fibroblastoma]], [[granulocytic sarcoma]], [[Kaposi’s sarcoma]], [[liposarcoma]], [[malignant fibrous histiocytoma]], malignant peripheral nerve sheath tumors, mengingeal [[hemangiopericytoma]]s, [[meningioma]]s, [[neurofibroma]]s, [[schwannoma]]s, and [[papillary thyroid carcinoma]].
A negative CD34 may exclude [[Ewing's sarcoma]]/PNET, [[myofibrosarcoma]] of the breast, and [[inflammatory myofibroblastic tumor]]s of the stomach.
Injection of CD34+ [[hematopoietic]] stem cells has been clinically applied to treat various diseases including spinal cord injury,<ref name = "Srivastava_2010">{{Cite journal|vauthors=Srivastava A, Bapat M, Ranade S, Srinivasan V, Murugan P, Manjunath S, Thamaraikannan P, Abraham S | title = Autologous Multiple Injections of in Vitro Expanded Autologous Bone Marrow Stem Cells For Cervical Level Spinal Cord Injury - A Case Report | journal = Journal of Stem Cells and Regenerative Medicine |year = 2010 | url = http://www.pubstemcell.com/monthly/006030700113.htm}}</ref> liver cirrhosis<ref name = "Terai_2006">{{cite journal | vauthors = Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I | title = Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy | journal = Stem Cells | volume = 24 | issue = 10 | pages = 2292–8 | date = Oct 2006 | pmid = 16778155 | doi = 10.1634/stemcells.2005-0542 }}</ref> and peripheral vascular disease.<ref name="pmid21671823">{{cite journal | vauthors = Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, Senthilkumar R, Murugan P, Srinivasan VR, Abraham S | title = Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience | journal = Cytotherapy | volume = 13 | issue = 8 | pages = 993–9 | date = Sep 2011 | pmid = 21671823 | doi = 10.3109/14653249.2011.579961 }}</ref>
== Interactions ==
CD34 has been shown to [[Protein-protein interaction|interact]] with [[CRKL]].<ref name=pmid11389015>{{cite journal | vauthors = Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ | title = The adapter protein CrkL associates with CD34 | journal = Blood | volume = 97 | issue = 12 | pages = 3768–75 | date = Jun 2001 | pmid = 11389015 | doi = 10.1182/blood.V97.12.3768 }}</ref>  It also [[Protein-protein interaction|interacts]] with [[L-selectin]], important in [[inflammation]].
== See also ==
* [[Cluster of differentiation]]
* [[List of histologic stains that aid in diagnosis of cutaneous conditions]]
== References ==
{{Reflist|35em}}
== Further reading ==
{{Refbegin|35em}}
* {{cite journal | vauthors = Bellini A, Mattoli S | title = The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses | journal = Laboratory Investigation | volume = 87 | issue = 9 | pages = 858–70 | date = Sep 2007 | pmid = 17607298 | doi = 10.1038/labinvest.3700654 }}
* {{cite journal | vauthors = Simmons DL, Satterthwaite AB, Tenen DG, Seed B | title = Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells | journal = Journal of Immunology | volume = 148 | issue = 1 | pages = 267–71 | date = Jan 1992 | pmid = 1370171 | doi =  | url = http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=1370171 }}
* {{cite journal | vauthors = Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG | title = Structure of the gene encoding CD34, a human hematopoietic stem cell antigen | journal = Genomics | volume = 12 | issue = 4 | pages = 788–94 | date = Apr 1992 | pmid = 1374051 | doi = 10.1016/0888-7543(92)90310-O }}
* {{cite journal | vauthors = Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, Sutherland DR, Baker MA, Greaves MF | title = Expression of the CD34 gene in vascular endothelial cells | journal = Blood | volume = 75 | issue = 12 | pages = 2417–26 | date = Jun 1990 | pmid = 1693532 | doi =  }}
* {{cite journal | vauthors = Fackler MJ, Civin CI, Sutherland DR, Baker MA, May WS | title = Activated protein kinase C directly phosphorylates the CD34 antigen on hematopoietic cells | journal = The Journal of Biological Chemistry | volume = 265 | issue = 19 | pages = 11056–61 | date = Jul 1990 | pmid = 1694174 | doi =  | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1694174 }}
* {{cite journal | vauthors = Sutherland DR, Watt SM, Dowden G, Karhi K, Baker MA, Greaves MF, Smart JE | title = Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34 | journal = Leukemia | volume = 2 | issue = 12 | pages = 793–803 | date = Dec 1988 | pmid = 2462139 | doi =  }}
* {{cite journal | vauthors = Nakamura Y, Komano H, Nakauchi H | title = Two alternative forms of cDNA encoding CD34 | journal = Experimental Hematology | volume = 21 | issue = 2 | pages = 236–42 | date = Feb 1993 | pmid = 7678811 | doi =  | id = {{INIST|4784611}} }}
* {{cite journal | vauthors = Huyhn A, Dommergues M, Izac B, Croisille L, Katz A, Vainchenker W, Coulombel L | title = Characterization of hematopoietic progenitors from human yolk sacs and embryos | journal = Blood | volume = 86 | issue = 12 | pages = 4474–85 | date = Dec 1995 | pmid = 8541536 | doi =  | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=8541536 }}
* {{cite journal | vauthors = Tavian M, Coulombel L, Luton D, Clemente HS, Dieterlen-Lièvre F, Péault B | title = Aorta-associated CD34+ hematopoietic cells in the early human embryo | journal = Blood | volume = 87 | issue = 1 | pages = 67–72 | date = Jan 1996 | pmid = 8547678 | doi =  | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=8547678 }}
* {{cite journal | vauthors = Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M | title = Generation and analysis of 280,000 human expressed sequence tags | journal = Genome Research | volume = 6 | issue = 9 | pages = 807–28 | date = Sep 1996 | pmid = 8889549 | doi = 10.1101/gr.6.9.807 }}
* {{cite journal | vauthors = Uchida N, Yang Z, Combs J, Pourquié O, Nguyen M, Ramanathan R, Fu J, Welply A, Chen S, Weddell G, Sharma AK, Leiby KR, Karagogeos D, Hill B, Humeau L, Stallcup WB, Hoffman R, Tsukamoto AS, Gearing DP, Péault B | title = The characterization, molecular cloning, and expression of a novel hematopoietic cell antigen from CD34+ human bone marrow cells | journal = Blood | volume = 89 | issue = 8 | pages = 2706–16 | date = Apr 1997 | pmid = 9108388 | doi =  | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9108388 }}
* {{cite journal | vauthors = Ruiz ME, Cicala C, Arthos J, Kinter A, Catanzaro AT, Adelsberger J, Holmes KL, Cohen OJ, Fauci AS | title = Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection by HIV | journal = Journal of Immunology | volume = 161 | issue = 8 | pages = 4169–76 | date = Oct 1998 | pmid = 9780190 | doi =  }}
* {{cite journal | vauthors = Kees UR, Ford J | title = Synergistic action of stem-cell factor and interleukin-7 in a human immature T-cell line | journal = Immunology | volume = 96 | issue = 2 | pages = 202–6 | date = Feb 1999 | pmid = 10233696 | pmc = 2326741 | doi = 10.1046/j.1365-2567.1999.00674.x }}
* {{cite journal | vauthors = Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, Huang CC, Kannagi R, Rosen SD, Hemmerich S | title = Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin | journal = The Journal of Cell Biology | volume = 145 | issue = 4 | pages = 899–910 | date = May 1999 | pmid = 10330415 | pmc = 2133194 | doi = 10.1083/jcb.145.4.899 }}
* {{cite journal | vauthors = Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, Le Bousse-Kerdilès MC | title = Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival | journal = Blood | volume = 95 | issue = 3 | pages = 756–68 | date = Feb 2000 | pmid = 10648383 | doi =  | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=10648383 }}
* {{cite journal | vauthors = Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ | title = The adapter protein CrkL associates with CD34 | journal = Blood | volume = 97 | issue = 12 | pages = 3768–75 | date = Jun 2001 | pmid = 11389015 | doi = 10.1182/blood.V97.12.3768 }}
* {{cite journal | vauthors = Dobo I, Robillard N, Pineau D, Geneviève F, Piard N, Rapp MJ, Boasson M, Zandecki M, Hermouet S | title = Use of pathology-specific peripheral blood CD34 thresholds to predict leukapheresis CD34 content with optimal accuracy: a bicentric analysis of 299 leukaphereses | journal = Annals of Hematology | volume = 80 | issue = 11 | pages = 639–46 | date = Nov 2001 | pmid = 11757722 | doi = 10.1007/s002770100365 }}
* {{cite journal | vauthors = Hogan CJ, Shpall EJ, Keller G | title = Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 1 | pages = 413–8 | date = Jan 2002 | pmid = 11782553 | pmc = 117574 | doi = 10.1073/pnas.012336799 | id = {{INIST|13429907}} | bibcode = 2002PNAS...99..413H | jstor = 3057551 }}
* {{cite journal | vauthors = Krauter J, Hartl M, Hambach L, Kohlenberg A, Gunsilius E, Ganser A, Heil G | title = Receptor-mediated endocytosis of CD34 on hematopoietic cells after stimulation with the monoclonal antibody anti-HPCA-1 | journal = Journal of Hematotherapy & Stem Cell Research | volume = 10 | issue = 6 | pages = 863–71 | date = Dec 2001 | pmid = 11798512 | doi = 10.1089/152581601317210953 }}
* {{cite journal | vauthors = Okuno Y, Iwasaki H, Huettner CS, Radomska HS, Gonzalez DA, Tenen DG, Akashi K | title = Differential regulation of the human and murine CD34 genes in hematopoietic stem cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 9 | pages = 6246–51 | date = Apr 2002 | pmid = 11983914 | pmc = 122934 | doi = 10.1073/pnas.092027799 | bibcode = 2002PNAS...99.6246O | jstor = 3058657 }}
* {{cite journal | vauthors = Hotfilder M, Röttgers S, Rosemann A, Jürgens H, Harbott J, Vormoor J | title = Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal | journal = Blood | volume = 100 | issue = 2 | pages = 640–6 | date = Jul 2002 | pmid = 12091359 | doi = 10.1182/blood.V100.2.640 }}
{{Refend}}
==External links==
* {{MeshName|Antigens,+CD34}}
* [http://www.ebioscience.com/resources/mouse-cd-chart.htm Mouse CD Antigen Chart]
* [http://www.ebioscience.com/resources/human-cd-chart.htm Human CD Antigen Chart]
* {{UCSC gene info|CD34}}


{{Clusters of differentiation}}
{{Clusters of differentiation}}
{{DEFAULTSORT:Cd34}}
[[Category:Clusters of differentiation]]
[[Category:Clusters of differentiation]]
{{WikiDoc Sources}}
[[Category:Cell adhesion molecules]]

Latest revision as of 10:36, 8 December 2018

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CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.[1][2][3]

CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first described on hematopoietic stem cells independently by Civin et al. and Tindle et al.[4][5][6][7] as a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of hematopoietic stem cells to bone marrow extracellular matrix or directly to stromal cells. 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.[8]

Function

The CD34 protein is a member of a family of single-pass transmembrane sialomucin proteins that show expression on early hematopoietic and vascular-associated tissue.[9] However, little is known about its exact function.[10]

CD34 is also an important adhesion molecule and is required for T cells to enter lymph nodes. It is expressed on lymph node endothelia, whereas the L-selectin to which it binds is on the T cell.[11][12] 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.[13][14] Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors.[15][16] Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.[9][15]

Tissue distribution

Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as hematopoietic cells, or in mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels but not lymphatics (except pleural lymphatics), mast cells, a sub-population of dendritic cells (which are factor XIIIa-negative) in the interstitium and around the adnexa of dermis of skin, as well as cells in soft tissue tumors like DFSP, GIST, SFT, HPC, and to some degree in MPNSTs, etc. The presence of CD34 on non-hematopoietic cells in various tissues has been linked to progenitor and adult stem cell phenotypes.[8]

It is important to mention that Long-Term Hematopoietic Stem Cells (LT-HSCs) in mice and humans are the hematopoietic cells with the greatest self-renewal capacity.[citation needed] Human HSCs express the CD34 marker.[citation needed]

CD34 is expressed in roughly 20% of murine hematopoietic stem cells,[17] and can be stimulated and reversed.[18]

Clinical applications

CD34+ cells may be isolated from blood samples using immunomagnetic or immunofluorescent methods.

Antibodies are used to quantify and purify hematopoietic progenitor stem cells for research and for clinical bone marrow transplantation. However, counting CD34+ mononuclear cells may overestimate myeloid blasts in bone marrow smears due to hematogones (B lymphocyte precursors) and CD34+ megakaryocytes.

Cells observed as CD34+ and CD38- are of an undifferentiated, primitive form; i.e., they are multipotential hemopoietic stem cells. Thus, because of their CD34+ expression, such undifferentiated cells can be sorted out.

In tumors, CD34 is found in alveolar soft part sarcoma, preB-ALL (positive in 75%), AML (40%), AML-M7 (most), dermatofibrosarcoma protuberans, gastrointestinal stromal tumors, giant cell fibroblastoma, granulocytic sarcoma, Kaposi’s sarcoma, liposarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumors, mengingeal hemangiopericytomas, meningiomas, neurofibromas, schwannomas, and papillary thyroid carcinoma.

A negative CD34 may exclude Ewing's sarcoma/PNET, myofibrosarcoma of the breast, and inflammatory myofibroblastic tumors of the stomach.

Injection of CD34+ hematopoietic stem cells has been clinically applied to treat various diseases including spinal cord injury,[19] liver cirrhosis[20] and peripheral vascular disease.[21]

Interactions

CD34 has been shown to interact with CRKL.[22] It also interacts with L-selectin, important in inflammation.

See also

References

  1. ↑ "Entrez Gene: CD34 CD34 molecule".
  2. ↑ Simmons DL, Satterthwaite AB, Tenen DG, Seed B (Jan 1992). "Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells". Journal of Immunology. 148 (1): 267–71. PMID 1370171.
  3. ↑ Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (Apr 1992). "Structure of the gene encoding CD34, a human hematopoietic stem cell antigen". Genomics. 12 (4): 788–94. doi:10.1016/0888-7543(92)90310-O. PMID 1374051.
  4. ↑ Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (1984). "Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells". Journal of Immunology. 133 (1): 157–65. PMID 6586833.
  5. ↑ Tindle RW. Nichols R. Chan L. Campana D. Birnie GD. (1985). "A novel monoclonal antibody BI-3C5 recognises myeloblasts and non-B, non-T lymphoblasts in acute leukaemia and CGL blast crises, and react with immature cells in normal bone marrow". Leukemia Research. 9: 1–9. doi:10.1016/0145-2126(85)90016-5.
  6. ↑ Tindle RW. Katz F. Martin H. Watt D. Catovsky D. Janossy G. Greaves M. (1987). "BI-3C5 (CD34) defines multipotential and lineage restricted progenitor cells and their leukaemic counterparts". In 'Leucocyte typing 111: White cell differentiation antigens. Oxford University Press, 654-655.
  7. ↑ Loken M. Shah V. Civin CI.. (1987). "Characterization of myeloid antigens on human bone marrow using multicolour immunofluorescence". In: McMichael, Leucocyte Typing III:White cell differentiation antigens.Oxford University Press 630-635.
  8. ↑ 8.0 8.1 Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A (Jun 2014). "Concise review: evidence for CD34 as a common marker for diverse progenitors". Stem Cells. 32 (6): 1380–9. doi:10.1002/stem.1661. PMC 4260088. PMID 24497003.
  9. ↑ 9.0 9.1 Nielsen JS, McNagny KM (Nov 2008). "Novel functions of the CD34 family". Journal of Cell Science. 121 (Pt 22): 3683–92. doi:10.1242/jcs.037507. PMID 18987355.
  10. ↑ Furness SG, McNagny K (2006). "Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis". Immunologic Research. 34 (1): 13–32. doi:10.1385/IR:34:1:13. PMID 16720896.
  11. ↑ Berg EL, Mullowney AT, Andrew DP, Goldberg JE, Butcher EC (Feb 1998). "Complexity and differential expression of carbohydrate epitopes associated with L-selectin recognition of high endothelial venules". The American Journal of Pathology. 152 (2): 469–77. PMC 1857953. PMID 9466573.
  12. ↑ Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J (Jul 2007). "Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis". The American Journal of Gastroenterology. 102 (7): 1499–509. doi:10.1111/j.1572-0241.2007.01189.x. PMID 17459027.
  13. ↑ Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM (Jan 2005). "CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution". Immunity. 22 (1): 43–57. doi:10.1016/j.immuni.2004.11.014. PMID 15664158.
  14. ↑ Strilić B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E (Oct 2009). "The molecular basis of vascular lumen formation in the developing mouse aorta". Developmental Cell. 17 (4): 505–15. doi:10.1016/j.devcel.2009.08.011. PMID 19853564.
  15. ↑ 15.0 15.1 Blanchet MR, Maltby S, Haddon DJ, Merkens H, Zbytnuik L, McNagny KM (Sep 2007). "CD34 facilitates the development of allergic asthma". Blood. 110 (6): 2005–12. doi:10.1182/blood-2006-12-062448. PMID 17557898.
  16. ↑ Blanchet MR, Bennett JL, Gold MJ, Levantini E, Tenen DG, Girard M, Cormier Y, McNagny KM (Sep 2011). "CD34 is required for dendritic cell trafficking and pathology in murine hypersensitivity pneumonitis". American Journal of Respiratory and Critical Care Medicine. 184 (6): 687–98. doi:10.1164/rccm.201011-1764OC. PMC 3208601. PMID 21642249.
  17. ↑ Ogawa M, Tajima F, Ito T, Sato T, Laver JH, Deguchi T (Jun 2001). "CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations". Annals of the New York Academy of Sciences. 938: 139–45. Bibcode:2001NYASA.938..139O. doi:10.1111/j.1749-6632.2001.tb03583.x. PMID 11458501.
  18. ↑ Tajima F, Sato T, Laver JH, Ogawa M (Sep 2000). "CD34 expression by murine hematopoietic stem cells mobilized by granulocyte colony-stimulating factor". Blood. 96 (5): 1989–93. PMID 10961905.
  19. ↑ Srivastava A, Bapat M, Ranade S, Srinivasan V, Murugan P, Manjunath S, Thamaraikannan P, Abraham S (2010). "Autologous Multiple Injections of in Vitro Expanded Autologous Bone Marrow Stem Cells For Cervical Level Spinal Cord Injury - A Case Report". Journal of Stem Cells and Regenerative Medicine.
  20. ↑ Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I (Oct 2006). "Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy". Stem Cells. 24 (10): 2292–8. doi:10.1634/stemcells.2005-0542. PMID 16778155.
  21. ↑ Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, Senthilkumar R, Murugan P, Srinivasan VR, Abraham S (Sep 2011). "Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience". Cytotherapy. 13 (8): 993–9. doi:10.3109/14653249.2011.579961. PMID 21671823.
  22. ↑ Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (Jun 2001). "The adapter protein CrkL associates with CD34". Blood. 97 (12): 3768–75. doi:10.1182/blood.V97.12.3768. PMID 11389015.

Further reading

External links

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