CD33

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	Wikidata
View/Edit Human

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.^[1] It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.^[2]

It binds sialic acids, therefore is a member of the SIGLEC family of lectins.

Structure

The extracellular portion of this receptor contains two immunoglobulin domains (one IgV and one IgC2 domain), placing CD33 within the immunoglobulin superfamily. The intracellular portion of CD33 contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that are implicated in inhibition of cellular activity.^[3]

Clinical significance

CD33 is the target of gemtuzumab ozogamicin (trade name: Mylotarg®; Pfizer/Wyeth-Ayerst Laboratories), ^[4] 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).^[5] On September 1, 2017, the FDA approved Pfizer's Mylotarg. ^[6]

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. ^[7] ^[8] ^[9]

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.^[10]

References

↑ 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 (Feb 2005). "Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells". Blood. 105 (3): 1256–64. doi:10.1182/blood-2004-06-2416. PMID 15388576.
↑ Hernández-Caselles T, Martínez-Esparza M, Pérez-Oliva AB, Quintanilla-Cecconi AM, García-Alonso A, Alvarez-López DM, García-Peñarrubia P (Jan 2006). "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 of Leukocyte Biology. 79 (1): 46–58. doi:10.1189/jlb.0205096. PMID 16380601.
↑ Myeloid cell surface antigen CD33 precursor - Homo sapiens (Human)
↑ Walter RB, Gooley TA, van der Velden VH, Loken MR, van Dongen JJ, Flowers DA, Bernstein ID, Appelbaum FR (May 2007). "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". Blood. 109 (10): 4168–70. doi:10.1182/blood-2006-09-047399. PMC 1885511. PMID 17227830.
↑ Calicheamicin (LL-E33288 antibiotics); ADC Review / Journal of Antibody-drug Conjugates (March 20, 2015)
↑ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm
↑ Gemtuzumab ozogamicin (Mylotarg®) Drug Description; ADC Review / Journal of Antibody-drug Conjugates (July 19, 2015)
↑ Pfizer Voluntarily Withdraws Cancer Treatment Mylotarg from U.S. Market; FDA Press Release (June 21, 2010)
↑ https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm
↑ Vadastuximab Talirine (SGN CD33a) Drug Description; ADC Review / Journal of Antibody-drug Conjugates (November 23, 2015)

External links

Human CD33 genome location and CD33 gene details page in the UCSC Genome Browser.

[pmid15388576-1] 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 (Feb 2005). "Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells". Blood. 105 (3): 1256–64. doi:10.1182/blood-2004-06-2416. PMID 15388576.

[pmid16380601-2] Hernández-Caselles T, Martínez-Esparza M, Pérez-Oliva AB, Quintanilla-Cecconi AM, García-Alonso A, Alvarez-López DM, García-Peñarrubia P (Jan 2006). "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 of Leukocyte Biology. 79 (1): 46–58. doi:10.1189/jlb.0205096. PMID 16380601.

[3] Myeloid cell surface antigen CD33 precursor - Homo sapiens (Human)

[pmid17227830-4] Walter RB, Gooley TA, van der Velden VH, Loken MR, van Dongen JJ, Flowers DA, Bernstein ID, Appelbaum FR (May 2007). "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". Blood. 109 (10): 4168–70. doi:10.1182/blood-2006-09-047399. PMC 1885511. PMID 17227830.

[5] Calicheamicin (LL-E33288 antibiotics); ADC Review / Journal of Antibody-drug Conjugates (March 20, 2015)

[6] ttps://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm

[7] Gemtuzumab ozogamicin (Mylotarg®) Drug Description; ADC Review / Journal of Antibody-drug Conjugates (July 19, 2015)

[8] Pfizer Voluntarily Withdraws Cancer Treatment Mylotarg from U.S. Market; FDA Press Release (June 21, 2010)

[9] ttps://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574507.htm

[10] Vadastuximab Talirine (SGN CD33a) Drug Description; ADC Review / Journal of Antibody-drug Conjugates (November 23, 2015)

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v t e Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1-50	CD1 a-c 1A 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151-200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

v t e Protein: cell membrane proteins (other than Cell surface receptor, enzymes, and cytoskeleton)
Arrestin	SAG ARRB1 ARRB2 ARR3
Membrane-spanning 4A	MS4A1 MS4A2 MS4A3 MS4A4A MS4A4E MS4A5 MS4A6A MS4A6E MS4A7 MS4A8B MS4A9 MS4A10 MS4A12 MS4A13 MS4A14 MS4A15 MS4A18
Myelin	Myelin basic protein PMP2 Myelin proteolipid protein PLP1 Myelin oligodendrocyte glycoprotein Myelin-associated glycoprotein Myelin protein zero
Pulmonary surfactant	Pulmonary surfactant-associated protein B Pulmonary surfactant-associated protein C
Tetraspanin	TSPAN1 TSPAN2 TSPAN3 TSPAN4 TSPAN5 TSPAN6 TSPAN7 TSPAN8 TSPAN9 TSPAN10 TSPAN11 TSPAN12 TSPAN13 TSPAN14 TSPAN15 TSPAN16 TSPAN17 TSPAN18 TSPAN19 TSPAN20 TSPAN21 TSPAN22 TSPAN23 TSPAN24 TSPAN25 TSPAN26 TSPAN27 TSPAN28 TSPAN29 TSPAN30 TSPAN31 TSPAN32 TSPAN33 TSPAN34
Other/ungrouped	Calnexin LDL-receptor-related protein-associated protein Neurofibromin 2 Presenilin PSEN1 PSEN2 HFE Phospholipid transfer proteins Dysferlin STRC OTOF
see also other cell membrane protein disorders

CD33

Contents

Structure

Clinical significance

References

External links

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