CD33

2018-06-05T02:39:31Z

2601:19B:B00:5F43:5192:3B61:B257:788D:

{{Infobox_gene}}

'''CD33''' or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a [[transmembrane receptor]] expressed on cells of [[myeloid]] lineage.<ref name="pmid15388576">{{cite journal | vauthors = Garnache-Ottou F, Chaperot L, Biichle S, Ferrand C, Remy-Martin JP, Deconinck E, de Tailly PD, Bulabois B, Poulet J, Kuhlein E, Jacob MC, Salaun V, Arock M, Drenou B, Schillinger F, Seilles E, Tiberghien P, Bensa JC, Plumas J, Saas P | title = Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells | journal = Blood | volume = 105 | issue = 3 | pages = 1256–64 | date = Feb 2005 | pmid = 15388576 | doi = 10.1182/blood-2004-06-2416 | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=15388576 }}</ref> It is usually considered myeloid-specific, but it can also be found on some [[lymphoid]] cells.<ref name="pmid16380601">{{cite journal | vauthors = Hernández-Caselles T, Martínez-Esparza M, Pérez-Oliva AB, Quintanilla-Cecconi AM, García-Alonso A, Alvarez-López DM, García-Peñarrubia P | title = A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing | journal = Journal of Leukocyte Biology | volume = 79 | issue = 1 | pages = 46–58 | date = Jan 2006 | pmid = 16380601 | doi = 10.1189/jlb.0205096 | url = http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=16380601 }}</ref>

It binds sialic acids, therefore is a member of the [[SIGLEC]] family of [[lectin]]s.

==Structure==
The extracellular portion of this receptor contains two [[immunoglobulin domain]]s (one IgV and one IgC2 domain), placing CD33 within the [[immunoglobulin superfamily]]. The intracellular portion of CD33 contains [[immunoreceptor tyrosine-based inhibitory motif]]s (ITIMs) that are implicated in inhibition of cellular activity.<ref>[http://www.ebi.uniprot.org/uniprot-srv/uniProtView.do?proteinAc=P20138 Myeloid cell surface antigen CD33 precursor - Homo sapiens (Human)]</ref>

==Clinical significance==
CD33 is the target of [[gemtuzumab ozogamicin]] (trade name: Mylotarg®; Pfizer/Wyeth-Ayerst Laboratories), <ref name="pmid17227830">{{cite journal | vauthors = Walter RB, Gooley TA, van der Velden VH, Loken MR, van Dongen JJ, Flowers DA, Bernstein ID, Appelbaum FR | title = CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy | journal = Blood | volume = 109 | issue = 10 | pages = 4168–70 | date = May 2007 | pmid = 17227830 | pmc = 1885511 | doi = 10.1182/blood-2006-09-047399 | url = http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=17227830 }}</ref> an [[Antibody-drug conjugate]] for the treatment of patients with [[acute myeloid leukemia]]. The drug is a recombinant, humanized anti-CD33 monoclonal antibody (IgG4 κ antibody hP67.6) covalently attached to the cytotoxic antitumor antibiotic calicheamicin (N-acetyl-γ-calicheamicin) via a bifunctional linker (4-(4-acetylphenoxy)butanoic acid).<ref>[http://adcreview.com/adc-university/adcs-101/cytotoxic-agents/calicheamicin/ Calicheamicin (LL-E33288 antibiotics); ADC Review / Journal of Antibody-drug Conjugates (March 20, 2015) ]</ref>
On September 1, 2017, the FDA approved Pfizer's Mylotarg. <ref>https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm</ref>

Gemtuzumab ozogamicin was initially approved by the [[U.S. Food and Drug Administration]] in 2000. However, during post marketing clinical trials researchers noticed a greater number of deaths in the group of patients who received gemtuzumab ozogamicin compared with those receiving chemotherapy alone. Based on these results, [[Pfizer]] voluntarily withdrew gemtuzumab ozogamicin from the market in mid-2010, but was reintroduced to the market in 2017. <ref>[http://adcreview.com/gemtuzumab-ozogamicin-mylotarg/ Gemtuzumab ozogamicin (Mylotarg®) Drug Description; ADC Review / Journal of Antibody-drug Conjugates (July 19, 2015)] </ref> <ref>[http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm216448.htm Pfizer Voluntarily Withdraws Cancer Treatment Mylotarg from U.S. Market; FDA Press Release (June 21, 2010)]</ref> <ref> https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm </ref>

CD33 is also the target in [[Vadastuximab talirine (SGN-CD33A)]], a novel [[antibody-drug conjugate]] being developed by [[Seattle Genetics]], utilizing this company's ADC technology.<ref>[http://adcreview.com/vadastuximab-talirine-sgn-cd33a-drug-description/ Vadastuximab Talirine (SGN CD33a) Drug Description; ADC Review / Journal of Antibody-drug Conjugates (November 23, 2015)]</ref>

== References ==
{{reflist|2}}

==External links==
* {{UCSC gene info|CD33}}

{{clusters of differentiation}}
{{Clusters of differentiation by lineage}}
{{lectins}}
{{Membrane proteins}}

[[Category:Lectins]]
[[Category:SIGLEC]]

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CD33