Disease relevance of CD99

• We conclude that staining formalin-fixed, paraffin-embedded, high-grade lymphomas with anti-cyclin D-1 antibody is useful in confirming the diagnosis of MCL-BV, whereas positive reactions with CD99, CD34, and particularly TdT are more characteristic of LBL [1].
• Earlier report showed that expression of a splice variant of CD99 transmembrane protein increases invasive ability of human breast cancer cells [2].
• Solitary sclerotic fibroma of skin: a possible link with pleomorphic fibroma with immunophenotypic expression for O13 (CD99) and CD34 [3].
• Myelodysplastic syndromes and normal bone marrow specimens were uniformly CD99 negative [4].
• A more recent study showed that 43% of acute myeloid leukemias (AMLs) and 55% of chloromas express CD99, concluding that CD99 is commonly expressed in AML and rarely seen in myeloproliferative disorders, myelodysplastic syndromes, or normal bone marrow [4].
• A mechanistic analysis of CD99-transfected osteosarcoma cells points to involvement of c-Src family kinase activity in regulating CD99 functions in malignancy [5].

Psychiatry related information on CD99

• Lower cotransfer of the more distant X-linked gene, MIC-2, was statistically significant in this kindred, but not in other patients with familial Alzheimer's disease [6].
• We investigated linkage between schizophrenia and the loci DXYS14, DXYS17, and MIC2 within the pseudoautosomal region in 85 families with two or more siblings suffering from schizophrenia or schizoaffective disorder [7].

High impact information on CD99

• Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp [8].
• The predicted amino acid sequence of the 540 bp coding region is 48% homologous to 12E7, the product of MIC2 [8].
• Previously we have shown that the pseudoautosomal gene MIC2 only rarely recombines between the sex chromosomes and, based on the elevated recombination rates in the pseudoautosomal region, we predicted that this gene would lie close to the Y-specific region [9].
• The X-located homologue, MIC2X, escapes X-inactivation and the equivalent Y-located locus, MIC2Y, was one of the first genes shown to reside on a mammalian Y chromosome [10].
• By using a bacterial expression system we have previously cloned a complementary DNA sequence corresponding to a MIC2 gene and have used this probe to show that the MIC2X and MIC2Y loci are closely related, if not identical [10].

Chemical compound and disease context of CD99

• ER and AR were never expressed by SFT or by chronic pleuritis, whereas PR were demonstrated in 2/16 "large" (>8 cm) and in 6/16 "small" (< or =8 cm) pleural SFT (all expressing CD34, bcl-2 and CD99) [11].
• The monoclonal antibody 013, which detects the cell surface glycoprotein p30/32mic2 (CD99) is a characteristic, if nonspecific, marker for peripheral neuroepithelioma and Ewing's sarcoma [12].
• Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing's sarcoma [13].
• Sixty recent Streptococcus pneumoniae isolates with different susceptibilities to ciprofloxacin (14 with MIC 0.5 mg/L, 10 with MIC 1 mg/L, eight with MIC 2 mg/L, 11 with MIC 4 mg/L and 17 with MIC > or =8 mg/L) were tested against five new quinolones using Todd-Hewitt broth with and without 80% serum [14].
• One hybridoma produced an IgM antibody (12E7) which recognized the capsular polysaccharide in ELISA and specifically labelled all tested Hib strains in immune fluorescent microscopy [15].

Biological context of CD99

• Human CD99 (MIC2) is a 32 kDa cell surface protein and its encoding gene is localized to the pseudoautosomal regions of both Xp and Yp chromosomes [16].
• On the basis of these findings, we suggest that CD99 belongs to the ancient PAR genes, and that the rapid interspecies divergence of its present sequence and map position is due to a high recombination frequency and the occurrence of chromosomal translocation, supporting the addition-attrition hypothesis for PAR evolution [17].
• Amino acid sequence alignment revealed five putative functional regions highly conserved between CD99L2 and CD99, indicating a close relationship between the two genes [16].
• Quantitative differences were confirmed by Western blot analysis of red cell membrane preparations from individuals of different Xga and CD99 phenotypes and by Northern blot analysis showing that the reticulocytes from CD99-L individuals expressed a reduced level of MIC2 transcripts compared to CD99-H donors [18].
• These results demonstrate that CD99 signal transduction can deliver effective costimulatory signals to T cells [19].

Anatomical context of CD99

• No evidence of association or complex formation between XG and CD99 proteins could be proven, either on transfected RAG cells or on human erythrocytes [20].
• A role for CD99 in T cell activation [19].
• Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells [2].
• In addition, in our experience, CD99 should be routinely evaluated on bone marrow clots, owing to decreased reactivity or loss of reactivity in rapid decalcifying (RDO) solution-decalcified specimens [4].
• CD99 is a cell surface molecule involved in the aggregation of lymphocytes and apoptosis of immature cortical thymocytes [21].

Associations of CD99 with chemical compounds

• Ligation of CD99 resulted in the pronounced tyrosine phosphorylation of an approximately 29-kDa protein suggesting that a specific CD99-induced signal transduction pathway may exist [19].
• A new mAb to these CD99 epitopes, Ad20, induces programmed cell death of transformed T cells as determined by morphological changes, phosphatidylserine exposure on the cell surface, and uptake of propidium iodide [22].
• Engagement of CD99 triggers the exocytic transport of ganglioside GM1 and the reorganization of actin cytoskeleton [23].
• Association of CD99 with actin cytoskeleton was inhibited by methyl-beta-cyclodextrin, while CD99-mediated GM1 clustering was inhibited by cytochalasin D [23].
• Phenotypically, the tumor cells consistently expressed vimentin, CD99, and both estrogen and progesterone receptors [24].

Regulatory relationships of CD99

• In general, ligation of CD99 induced kinetically faster and more profound death responses as compared with the impact of anti-Fas and TNF-related apoptosis-inducing ligand (TRAIL) [22].
• Treatment of ES cells with zyxin antisense oligonucleotides inhibited CD99-induced cell aggregation and apoptosis, suggesting a functional role for this protein [25].
• Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive [26].
• Gingipains of Porphyromonas gingivalis modulate leukocyte adhesion molecule expression induced in human endothelial cells by ligation of CD99 [27].
• Ligation of CD99 on endothelial cells was shown to induce expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and major histocompatibility complex class II molecules and to increase adhesion of leukocytes [27].

Other interactions of CD99

• Unlike the rapidly evolved CD99 gene, these CD99L2 genes were highly conserved among those species [16].
• These findings suggest that the phenotypic relationship between XG and CD99 is mostly regulated at the transcriptional level, but they do not formally exclude some posttranscriptional effect [20].
• These findings further support the hypothesis of a single genetic control of CD99 and Xga expression by the XGR locus [18].
• These results show that CD99 has a costimulatory function for T cells and acts by a mechanism distinct from CD28 [28].
• Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1 [17].

Analytical, diagnostic and therapeutic context of CD99

• As a preliminary study of this phenomenon, human XG and CD99 recombinant proteins were expressed in murine RAG cells and analyzed by flow cytometry [20].
• Overexpression of zyxin after CD99 ligation was confirmed by real-time PCR and Western blot [25].
• In conclusion, although inhibin-alpha and PLAP, and, to a somewhat lesser extent, CD99 and HEA125 immunostaining are helpful in the differential diagnosis of certain testicular neoplasms that are difficult to distinguish on morphologic grounds, chromogranin is far less helpful in this context [29].
• We evaluated CD99 expression and analysed Ki67 labelling by immunohistochemistry in PETs [30].
• The interaction between CD99 and CypA was confirmed by co-immunoprecipitation and confocal immunofluorescence studies [31].

References