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CD33  -  CD33 molecule

Homo sapiens

 
 
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Disease relevance of CD33

  • Thus, the present study suggests that p75/AIRM1 and CD33 may play a regulatory role in normal myelopoiesis and may be viewed as suitable target molecules to counteract the proliferation/survival of chronic myeloid leukemias [1].
  • Phenotypic analysis based on the expression of CD33, CD34 and CD38 before and after passage in NOD/SCID showed that in 10 out of 16 samples investigated phenotypes were different [2].
  • Anti-CD33 monoclonal antibodies enhance the cytotoxic effects of cytosine arabinoside and idarubicin on acute myeloid leukemia cells through similarities in their signaling pathways [3].
  • An MDS patient who had progressed from RA to RAEB showed further projecting pattern of expression of CD38 and CD33 in CD34(+)CD45(dull+)SSC(low) population in accordance with the disease progression [4].
  • The results show that HTLV-I immortalized cell lines coexpressed CD13, CD33 and lymphoid markers [5].
 

High impact information on CD33

  • Cells that expressed both CD11b and CD33 (antigens characteristic of mature and immature cells, respectively), and which were found by fluorescence in situ hybridization to carry the t(15;17) translocation, increased progressively in number during treatment and persisted in the early phase of complete remission [6].
  • The p67 cDNA encodes a 526-amino acid protein with acidic middle and carboxyl-terminal domains that are similar to a sequence motif found in the noncatalytic domain of src-related tyrosine kinases [7].
  • Recombinant p67 (r-p67) partially restored NADPH oxidase activity to p67-deficient neutrophil cytosol from these patients [7].
  • The highest amino acid sequence similarity has been found with the myeloid-specific CD33 molecule and the placental CD33L1 protein [8].
  • Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33 [9].
 

Chemical compound and disease context of CD33

 

Biological context of CD33

  • In this study, we show that p75/AIRM1 is also expressed by cells of the myelomonocytic cell lineage, in which it appears at a later stage as compared with CD33 [1].
  • These data indicate that CD33 is a phosphoprotein, that its phosphorylation may be controlled by PKC downstream of cytokine stimulation, and that its phosphorylation is cross-regulated with its lectin activity [14].
  • Donor cell engraftment was manifested by the presence of B (CD19+) and myeloid (CD33+) cells of donor HLA phenotype [15].
  • These results show that CD33 can function as a sialic acid-dependent cell adhesion molecule and that binding can be modulated by endogenous sialoglycoconjugates when CD33 is expressed in a plasma membrane [16].
  • A cDNA clone encoding the human myeloid Ag CD33 was isolated from a U937 cDNA library after three rounds of transient expression in COS cells and enrichment by panning [17].
 

Anatomical context of CD33

  • P75/AIRM1 is a recently identified surface molecule that belongs to the sialoadhesin family and displays homology with the myeloid cell antigen CD33 [1].
  • Unexpectedly, myeloid-specific cell surface antigens such as CD33 and CD13 and the early B-cell antigen identified by CD10 were expressed on a proportion of plasma cells [18].
  • However, CD33 was unable to mediate cell binding after transient expression in COS cells, despite high levels of surface expression [16].
  • A recombinant soluble form of CD33, Fc-CD33, bound red blood cells with a specificity similar to that of sialoadhesin, preferring NeuAc alpha 2,3Gal in N- and O-glycans over NeuAc alpha 2,6Gal in N-glycans [16].
  • The vast majority of intestinal HSCs coexpressed the T cell Ag, CD7 (92% in the epithelium, 80% in the lamina propria) whereas <10% coexpressed the myeloid Ag CD33, suggesting that gut HSCs are a relatively mature population committed to the lymphoid lineage [19].
 

Associations of CD33 with chemical compounds

  • Many of the Siglecs (including CD33) have been reported to be tyrosine phosphorylated in the cytosolic tails under specific stimulation conditions [14].
  • Inhibition of CD33 phosphorylation with pharmacologic agents resulted in an increase of sialic acid-dependent rosette formation [14].
  • Notably, although this is the first example of serine/threonine phosphorylation in the subfamily of CD33-like Siglecs, some of the other members also have putative target sites in their cytoplasmic tails [14].
  • The extracellular part of CD33 contains two Ig-like domains which are highly related to the first two domains of the neural cell myelin-associated glycoprotein and the B cell Ag CD22 [17].
  • These observations suggest that a single N-linked glycosylation site located at a similar position in the CD22 and CD33 glycoproteins is critical for regulating ligand recognition by both receptors [20].
 

Physical interactions of CD33

  • The CD33 antigen is a 67-kd glycosylated transmembrane protein of the sialic acid-binding immunoglobulinlike lectin (siglec) family with immunoreceptor tyrosine-based inhibitory motifs [21].
  • Analysis using mutants of SHP-1 demonstrated that binding Y340 of CD33 was primarily to the amino Src homology-2 domain of SHP-1 [22].
  • Cross-blocking of M195 binding by MY9 and L4F3 (CD33) was demonstrated [23].
  • In these cultured cells, engagement of CD33 resulted in an increased surface binding of annexin-V, followed by cell death [24].
  • The biochemical characteristics (m.w. and isoelectric point) of p67 are identical with those of the actin binding protein L-plastin (Fimbrin), a cytoplasmic protein that contains two Ca2+ binding sites and a calmodulin binding domain [25].
 

Enzymatic interactions of CD33

  • In this study, using peptide pull-down experiments, we found that SOCS3 can specifically bind to the phosphorylated ITIM of CD33 [11].
 

Regulatory relationships of CD33

  • Moreover, 93% of this CD34/CD7 double positive subpopulation co-expressed CD33 antigen in CML patients [26].
  • A higher proportion of PB-CD34+ cells expressed the CD33 myeloid antigen (84% v 43%) and expressed higher levels of the pan leukocyte antigen CD45 than BM-CD34+ cells [27].
  • We found that CD34(bright) cells regardless of their myeloid commitment were ICOSL(-), whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared [28].
  • A significantly greater proportion of CD33+ cells (55%) expressed CysLT1 receptor compared with CD123+ cells (11%) [29].
  • Most (87-98%) CFC generated in the LTMCs that were initiated with CD33-CD34+ cells were found to express the CD33 antigen [30].
 

Other interactions of CD33

  • SR-1Ad cells coexpress other progenitor-associated antigens in a combination reflecting the dominant presence of erythroid progenitors (high expression of CD34, DR, CD38, and Ep-1; low expression of CD33) [31].
  • A single N-linked glycosylation site is implicated in the regulation of ligand recognition by the I-type lectins CD22 and CD33 [20].
  • Expression of myeloid antigens (CD13 or CD33) were detected in nine of them, and remarkably, 18 cases (72%) displayed CD34 [32].
  • With respect to myeloid antigens, APLs less frequently expressed the myelomonocytic antigens, CD11b (p = 0.0001) and CD14 (p = 0.0013), whereas expression of CD33, a pan-myeloid marker, was more frequent in APL (p = 0.0001) [33].
  • B-cell antigen CD19 was found in two cases with CD7 solely as T-cell antigen, and these cases possessed CD13/CD33 [34].
 

Analytical, diagnostic and therapeutic context of CD33

References

  1. Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells. Vitale, C., Romagnani, C., Falco, M., Ponte, M., Vitale, M., Moretta, A., Bacigalupo, A., Moretta, L., Mingari, M.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Identification of variables determining the engraftment potential of human acute myeloid leukemia in the immunodeficient NOD/SCID human chimera model. Rombouts, W.J., Martens, A.C., Ploemacher, R.E. Leukemia (2000) [Pubmed]
  3. Anti-CD33 monoclonal antibodies enhance the cytotoxic effects of cytosine arabinoside and idarubicin on acute myeloid leukemia cells through similarities in their signaling pathways. Balaian, L., Ball, E.D. Exp. Hematol. (2005) [Pubmed]
  4. Comparative multi-color flow cytometric analysis of cell surface antigens in bone marrow hematopoietic progenitors between refractory anemia and aplastic anemia. Otawa, M., Kawanishi, Y., Iwase, O., Shoji, N., Miyazawa, K., Ohyashiki, K. Leuk. Res. (2000) [Pubmed]
  5. In vitro infection of CD4+ T lymphocytes with HTLV-I generates immortalized cell lines coexpressing lymphoid and myeloid cell markers. Tricarico, M., Macchi, B., D'Atri, S., Morrone, S., Bonmassar, E., Fuggetta, M.P., Graziani, G. Leukemia (1999) [Pubmed]
  6. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. Soignet, S.L., Maslak, P., Wang, Z.G., Jhanwar, S., Calleja, E., Dardashti, L.J., Corso, D., DeBlasio, A., Gabrilove, J., Scheinberg, D.A., Pandolfi, P.P., Warrell, R.P. N. Engl. J. Med. (1998) [Pubmed]
  7. Cloning of a 67-kD neutrophil oxidase factor with similarity to a noncatalytic region of p60c-src. Leto, T.L., Lomax, K.J., Volpp, B.D., Nunoi, H., Sechler, J.M., Nauseef, W.M., Clark, R.A., Gallin, J.I., Malech, H.L. Science (1990) [Pubmed]
  8. Identification and molecular cloning of p75/AIRM1, a novel member of the sialoadhesin family that functions as an inhibitory receptor in human natural killer cells. Falco, M., Biassoni, R., Bottino, C., Vitale, M., Sivori, S., Augugliaro, R., Moretta, L., Moretta, A. J. Exp. Med. (1999) [Pubmed]
  9. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. Grouard, G., Rissoan, M.C., Filgueira, L., Durand, I., Banchereau, J., Liu, Y.J. J. Exp. Med. (1997) [Pubmed]
  10. A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity. Caron, P.C., Jurcic, J.G., Scott, A.M., Finn, R.D., Divgi, C.R., Graham, M.C., Jureidini, I.M., Sgouros, G., Tyson, D., Old, L.J. Blood (1994) [Pubmed]
  11. CD33 responses are blocked by SOCS3 through accelerated proteasomal-mediated turnover. Orr, S.J., Morgan, N.M., Elliott, J., Burrows, J.F., Scott, C.J., McVicar, D.W., Johnston, J.A. Blood (2007) [Pubmed]
  12. Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia. Stiff, P.J., Schulz, W.C., Bishop, M., Marks, L. Blood (1991) [Pubmed]
  13. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Bross, P.F., Beitz, J., Chen, G., Chen, X.H., Duffy, E., Kieffer, L., Roy, S., Sridhara, R., Rahman, A., Williams, G., Pazdur, R. Clin. Cancer Res. (2001) [Pubmed]
  14. Role of protein kinase C in the phosphorylation of CD33 (Siglec-3) and its effect on lectin activity. Grobe, K., Powell, L.D. Blood (2002) [Pubmed]
  15. Engraftment of human hematopoietic precursor cells with secondary transfer potential in SCID-hu mice. Chen, B.P., Galy, A., Kyoizumi, S., Namikawa, R., Scarborough, J., Webb, S., Ford, B., Cen, D.Z., Chen, S.C. Blood (1994) [Pubmed]
  16. Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules. Freeman, S.D., Kelm, S., Barber, E.K., Crocker, P.R. Blood (1995) [Pubmed]
  17. Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells. Simmons, D., Seed, B. J. Immunol. (1988) [Pubmed]
  18. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Terstappen, L.W., Johnsen, S., Segers-Nolten, I.M., Loken, M.R. Blood (1990) [Pubmed]
  19. Detection and characterization of hemopoietic stem cells in the adult human small intestine. Lynch, L., O'donoghue, D., Dean, J., O'sullivan, J., O'farrelly, C., Golden-Mason, L. J. Immunol. (2006) [Pubmed]
  20. A single N-linked glycosylation site is implicated in the regulation of ligand recognition by the I-type lectins CD22 and CD33. Sgroi, D., Nocks, A., Stamenkovic, I. J. Biol. Chem. (1996) [Pubmed]
  21. CD33 as a target for selective ablation of acute myeloid leukemia. Bernstein, I.D. Clinical lymphoma. (2002) [Pubmed]
  22. Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. Paul, S.P., Taylor, L.S., Stansbury, E.K., McVicar, D.W. Blood (2000) [Pubmed]
  23. Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia. Scheinberg, D.A., Tanimoto, M., McKenzie, S., Strife, A., Old, L.J., Clarkson, B.D. Leukemia (1989) [Pubmed]
  24. Engagement of CD33 surface molecules prevents the generation of dendritic cells from both monocytes and CD34+ myeloid precursors. Ferlazzo, G., Spaggiari, G.M., Semino, C., Melioli, G., Moretta, L. Eur. J. Immunol. (2000) [Pubmed]
  25. Serine phosphorylation of a 67-kDa protein in human T lymphocytes represents an accessory receptor-mediated signaling event. Henning, S.W., Meuer, S.C., Samstag, Y. J. Immunol. (1994) [Pubmed]
  26. CD7 expression on CD34+ cells from chronic myeloid leukaemia in chronic phase. Martín-Henao, G.A., Quiroga, R., Sureda, A., García, J. Am. J. Hematol. (1999) [Pubmed]
  27. Identification and comparison of CD34-positive cells and their subpopulations from normal peripheral blood and bone marrow using multicolor flow cytometry. Bender, J.G., Unverzagt, K.L., Walker, D.E., Lee, W., Van Epps, D.E., Smith, D.H., Stewart, C.C., To, L.B. Blood (1991) [Pubmed]
  28. Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34(+) progenitor cells during differentiation into antigen presenting cells. Richter, G., Hayden-Ledbetter, M., Irgang, M., Ledbetter, J.A., Westermann, J., Körner, I., Daemen, K., Clark, E.A., Aicher, A., Pezzutto, A. J. Biol. Chem. (2001) [Pubmed]
  29. Role for cysteinyl leukotrienes in allergen-induced change in circulating dendritic cell number in asthma. Parameswaran, K., Liang, H., Fanat, A., Watson, R., Snider, D.P., O'Byrne, P.M. J. Allergy Clin. Immunol. (2004) [Pubmed]
  30. Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties. Andrews, R.G., Singer, J.W., Bernstein, I.D. J. Exp. Med. (1989) [Pubmed]
  31. Isolation of c-kit receptor-expressing cells from bone marrow, peripheral blood, and fetal liver: functional properties and composite antigenic profile. Papayannopoulou, T., Brice, M., Broudy, V.C., Zsebo, K.M. Blood (1991) [Pubmed]
  32. Genetic, phenotypic and clinical features of acute lymphoblastic leukemias expressing myeloperoxidase mRNA detected by RT-PCR. Serrano, J., Román, J., Jiménez, A., Castillejo, J.A., Navarro, J.A., Sánchez, J., García-Castellanos, J.M., Martín, C., Maldonado, J., Torres, A. Leukemia (1999) [Pubmed]
  33. The immunophenotype of acute promyelocytic leukemia (APL): an ECOG study. Paietta, E., Andersen, J., Gallagher, R., Bennett, J., Yunis, J., Cassileth, P., Rowe, J., Wiernik, P.H. Leukemia (1994) [Pubmed]
  34. Expression pattern of hybrid phenotype in adult acute lymphoblastic leukemia. Nakase, K., Kita, K., Miwa, H., Nishii, K., Shiku, H., Nasu, K., Dohy, H., Kyo, T., Kamada, N., Tsutani, H. Cancer Detect. Prev. (2001) [Pubmed]
  35. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. Terstappen, L.W., Huang, S., Safford, M., Lansdorp, P.M., Loken, M.R. Blood (1991) [Pubmed]
  36. 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. Hernández-Caselles, T., Martínez-Esparza, M., Pérez-Oliva, A.B., Quintanilla-Cecconi, A.M., García-Alonso, A., Alvarez-López, D.M., García-Peñarrubia, P. J. Leukoc. Biol. (2006) [Pubmed]
 
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