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

• M195 is a murine monoclonal antibody that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous leukemia) cells, but not normal stem cells [10].
• CD33 is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family of inhibitory receptors and a therapeutic target for acute myeloid leukemia (AML) [11].
• Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL [12].
• PURPOSE: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML) [13].

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

• Three color immunofluorescence experiments showed that all CD34+ BM cells that expressed the CD71, CD33, and CD10 antigens, concurrently stained brightly with anti-CD38 monoclonal antibodies (MoAbs) [35].
• Rosette formation by COS cells expressing a form of CD33 lacking its cytoplasmic domain was not affected by these same agents [14].
• Additionally, reverse transcriptase-polymerase chain reaction and Northern blot analysis showed an unknown CD33 isoform (CD33m) expressed on all CD33+ cell lines or T cell clones tested [36].
• MATERIALS AND METHODS: We investigated two AML cells lines and 14 primary AML samples for their proliferative response ((3)H-thymidine incorporation), colony formation, and biochemical (Western blot analysis) to anti-CD33 mAb treatment combined with chemotherapy agents [3].
• RESULTS: CD33 ligation induced a significant increase in ara-C- or IDA- but not VP-16-or Bryostatin-mediated inhibition of proliferation and colony formation [3].

References