CD34

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CD34 molecule
Identifiers
Symbol CD34
External IDs OMIM142230 MGI88329 HomoloGene1343 GeneCards: CD34 Gene
RNA expression pattern
PBB GE CD34 209543 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 947 12490
Ensembl ENSG00000174059 ENSMUSG00000016494
UniProt P28906 Q64314
RefSeq (mRNA) NM_001025109 NM_001111059
RefSeq (protein) NP_001020280 NP_001104529
Location (UCSC) Chr 1:
208.06 – 208.08 Mb
Chr 1:
194.94 – 194.96 Mb
PubMed search [1] [2]

Hematopoietic progenitor cell antigen CD34 also known as CD34 antigen is a protein that in humans is encoded by the CD34 gene.[1][2][3]

CD34 is a cluster of differentiation 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 stromal cells.

Function[edit]

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.[4] However, little is known about its exact function.[5]

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.[6][7] 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 lumens.[8][9] Finally, recent data suggest CD34 may also play a more selective role in chemokine-dependent migration of eosinophils and dendritic cell precursors.[10][11] Regardless of its mode of action, under all circumstances CD34, and its relatives podocalyxin and endoglycan, facilitates cell migration.[10][4]

Tissue distribution[edit]

Cells expressing CD34 (CD34+ cell) are normally found in the umbilical cord and bone marrow as hematopoietic cells, a subset of mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels but not lymphatics (except pleural lymphatics), mast cells, a sub-population 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.[12] 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. Human HSCs express CD34 marker but mice HSCs do not express CD34 marker.

Clinical applications[edit]

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,[13] Liver Cirrhosis[14] and Peripheral Vascular disease.[15] Research has shown that CD34+ cells are relatively more in men than in women in the reproductive age among Spinal Cord Injury victims.[16]

Interactions[edit]

CD34 has been shown to interact with CRKL.[17] It also interacts with L-selectin, important in inflammation.

See also[edit]

References[edit]

  1. ^ "Entrez Gene: CD34 CD34 molecule". 
  2. ^ Simmons DL, Satterthwaite AB, Tenen DG, Seed B (1 January 1992). "Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells". J. Immunol. 148 (1): 267–71. PMID 1370171. 
  3. ^ Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (April 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. ^ a b Nielsen JS, McNagny KM (2008). "Novel functions of the CD34 family". J of Cell Science 121 (Pt 22): 3682–3692. doi:10.1242/jcs.037507. PMID 18987355. 
  5. ^ Furness SG, McNagny K (2006). "Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis". Immunol. Res. 34 (1): 13–32. doi:10.1385/IR:34:1:13. PMID 16720896. 
  6. ^ Berg EL, Mullowney AT, Andrew DP, Goldberg JE, Butcher EC (February 1998). "Complexity and differential expression of carbohydrate epitopes associated with L-selectin recognition of high endothelial venules". Am. J. Pathol. 152 (2): 469–77. PMC 1857953. PMID 9466573. 
  7. ^ Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J (July 2007). "Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis". Am. J. Gastroenterol. 102 (7): 1499–509. doi:10.1111/j.1572-0241.2007.01189.x. PMID 17459027. 
  8. ^ Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM (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. 
  9. ^ Strilić B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E (2009). "The molecular basis of vascular lumen formation in the developing mouse aorta". Dev Cell 17 (4): 505–15. doi:10.1016/j.devcel.2009.08.011. PMID 19853564. 
  10. ^ a b Blanchet MR, Maltby S, Haddon DJ, Merkens H, Zbytnuik L, McNagny KM (2007). "CD34 facilitates the development of allergic asthma". BLOOD 110 (6): 2005–12. doi:10.1182/blood-2006-12-062448. PMID 17557898. 
  11. ^ Blanchet MR, Bennett JL, Gold MJ, Levantini E, Tenen DG, Girard M, Cormier Y, McNagny KM (2007). "CD34 is required for dendritic cell trafficking and pathology in murine hypersensitivity pneumonitis.". Am J Respir Crit Care Med. 184 (6): 687–98. doi:10.1164/rccm.201011-1764OC. PMID 21642249. 
  12. ^ Sidney LE, Branch MJ, Dunphy SE et al. (2014) Stem Cells.Concise review: Evidence for CD34 as a common marker for diverse progenitors. DOI: 10.1002/stem.1661. PMID 24497003.
  13. ^ 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. 
  14. ^ Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I (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. 
  15. ^ Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, Senthilkumar R, Murugan P, Srinivasan VR, Abraham S (September 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. 
  16. ^ Dedeepiya V, Rao Y Y, Jayakrishnan G, Parthiban JKBC, Baskar S, Manjunath S, Senthilkumar R and Abraham S (2012). "Index of CD34+ cells and mononuclear cells in the bone marrow of Spinal cord Injury patients of different age groups- A comparative analysis". Bone Marrow Research. 
  17. ^ 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[edit]

  • Bellini A, Mattoli S (September 2007). "The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses". Lab. Invest. 87 (9): 858–70. doi:10.1038/labinvest.3700654. PMID 17607298. 
  • Simmons DL, Satterthwaite AB, Tenen DG, Seed B (1992). "Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells". J. Immunol. 148 (1): 267–71. PMID 1370171. 
  • Satterthwaite AB, Burn TC, Le Beau MM, Tenen DG (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. 
  • Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, Sutherland DR, Baker MA, Greaves MF (1990). "Expression of the CD34 gene in vascular endothelial cells". Blood 75 (12): 2417–26. PMID 1693532. 
  • Fackler MJ, Civin CI, Sutherland DR, Baker MA, May WS (1990). "Activated protein kinase C directly phosphorylates the CD34 antigen on hematopoietic cells". J. Biol. Chem. 265 (19): 11056–61. PMID 1694174. 
  • Sutherland DR, Watt SM, Dowden G, Karhi K, Baker MA, Greaves MF, Smart JE (1989). "Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34". Leukemia 2 (12): 793–803. PMID 2462139. 
  • Nakamura Y, Komano H, Nakauchi H (1993). "Two alternative forms of cDNA encoding CD34". Exp. Hematol. 21 (2): 236–42. PMID 7678811. 
  • Huyhn A, Dommergues M, Izac B, Croisille L, Katz A, Vainchenker W, Coulombel L (1996). "Characterization of hematopoietic progenitors from human yolk sacs and embryos". Blood 86 (12): 4474–85. PMID 8541536. 
  • Tavian M, Coulombel L, Luton D, Clemente HS, Dieterlen-Lièvre F, Péault B (1996). "Aorta-associated CD34+ hematopoietic cells in the early human embryo". Blood 87 (1): 67–72. PMID 8547678. 
  • 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 (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549. 
  • 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 (1997). "The characterization, molecular cloning, and expression of a novel hematopoietic cell antigen from CD34+ human bone marrow cells". Blood 89 (8): 2706–16. PMID 9108388. 
  • Ruiz ME, Cicala C, Arthos J, Kinter A, Catanzaro AT, Adelsberger J, Holmes KL, Cohen OJ, Fauci AS (1998). "Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection by HIV". J. Immunol. 161 (8): 4169–76. PMID 9780190. 
  • Kees UR, Ford J (1999). "Synergistic action of stem-cell factor and interleukin-7 in a human immature T-cell line". Immunology 96 (2): 202–6. doi:10.1046/j.1365-2567.1999.00674.x. PMC 2326741. PMID 10233696. 
  • Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, Huang CC, Kannagi R, Rosen SD, Hemmerich S (1999). "Sulfotransferases of Two Specificities Function in the Reconstitution of High Endothelial Cell Ligands for L-selectin". J. Cell Biol. 145 (4): 899–910. doi:10.1083/jcb.145.4.899. PMC 2133194. PMID 10330415. 
  • Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, Le Bousse-Kerdilès MC (2000). "Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival". Blood 95 (3): 756–68. PMID 10648383. 
  • Felschow DM, McVeigh ML, Hoehn GT, Civin CI, Fackler MJ (2001). "The adapter protein CrkL associates with CD34". Blood 97 (12): 3768–75. doi:10.1182/blood.V97.12.3768. PMID 11389015. 
  • Dobo I, Robillard N, Pineau D, Geneviève F, Piard N, Rapp MJ, Boasson M, Zandecki M, Hermouet S (2001). "Use of pathology-specific peripheral blood CD34 thresholds to predict leukapheresis CD34 content with optimal accuracy: a bicentric analysis of 299 leukaphereses". Ann. Hematol. 80 (11): 639–46. doi:10.1007/s002770100365. PMID 11757722. 
  • Hogan CJ, Shpall EJ, Keller G (2002). "Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice". Proc. Natl. Acad. Sci. U.S.A. 99 (1): 413–8. doi:10.1073/pnas.012336799. PMC 117574. PMID 11782553. 
  • Krauter J, Hartl M, Hambach L, Kohlenberg A, Gunsilius E, Ganser A, Heil G (2003). "Receptor-mediated endocytosis of CD34 on hematopoietic cells after stimulation with the monoclonal antibody anti-HPCA-1". J. Hematother. Stem Cell Res. 10 (6): 863–71. doi:10.1089/152581601317210953. PMID 11798512. 
  • Okuno Y, Iwasaki H, Huettner CS, Radomska HS, Gonzalez DA, Tenen DG, Akashi K (2002). "Differential regulation of the human and murine CD34 genes in hematopoietic stem cells". Proc. Natl. Acad. Sci. U.S.A. 99 (9): 6246–51. doi:10.1073/pnas.092027799. PMC 122934. PMID 11983914. 
  • Hotfilder M, Röttgers S, Rosemann A, Jürgens H, Harbott J, Vormoor J (2002). "Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal". Blood 100 (2): 640–6. doi:10.1182/blood.V100.2.640. PMID 12091359. 

External links[edit]