Disease relevance of CD177

• The question arises whether this mutation is observed in those patients with ET and IMF who have also displayed previously described molecular markers, notably the ability to form endogenous erythroid colonies (EECs), overexpression of polycythemia rubra vera 1 (PRV-1), and decreased c-Mpl expression [1].
• We therefore analyzed the Janus kinase 2 (Jak2) DNA sequence, EEC growth, PRV-1 expression, and c-Mpl (myeloproliferative) levels in a cohort of 78 myeloproliferative disorder (MPD) patients (42 ET, 22 PV, and 14 IMF) [1].
• Only G-CSF-stimulated individuals and patients with severe bacterial infections and polycythaemia showed a significantly (P < 0.001) increased CD177 expression compared with healthy individuals, indicating that neutrophil CD177 expression can increase significantly in certain clinical conditions [2].
• Alloimmunization to the neutrophil antigen NB1 (HNA-2a, CD177) can result in immune neutropenia and transfusion-related acute lung injury [3].
• Moreover, PRV-1 is not expressed in mononuclear cells from patients with chronic myelogenous leukemia (n = 4) or acute myelogenous leukemia (n = 5) or in granulocytes from patients with essential thrombocythemia (n = 4) or secondary erythrocytosis (n = 4) [4].

High impact information on CD177

• Thus, measurement of serum erythropoietin in a single sample may be misleading and may not have high discriminatory value in distinguishing between polycythemia rubra vera and secondary erythrocytosis [5].
• X-linked somatic-cell selection and polycythemia rubra vera [6].
• Although some myeloproliferative disorders may transform into others, conversion of polycythemia rubra vera to chronic myelogenous leukemia has been denied [7].
• We report here an elderly man with polycythemia rubra vera and a normal leukocyte alkaline phosphatase who developed chronic myelogenous leukemia with a low leukocyte alkaline phosphatase and a marrow karyotype of 45, X, Ph1-positive [7].
• Evaluation excluded lung disease, shunt physiology, hemoglobin with increased oxygen affinity, erythropoietin-producing tumor, renal disease, or polycythemia rubra vera as the primary cause of erythrocytosis in these patients [8].

Chemical compound and disease context of CD177

• Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the pathogenesis of immune neutropenias and transfusion reactions [9].
• The uptake of CBDCA into L1210 (lymphosarcoma), CC531 (colonic carcinoma), COV413.B (human ovarian carcinoma) and NB1 (human neuroblastoma) cells was 1.5 to 13 times lower than the uptake of cDDP [10].
• Platelet-rich plasma serotonin levels in chronic myeloproliferative disorders: evaluation of diagnostic use and comparison with the neutrophil PRV-1 assay [11].
• In AP and polycythemia rubra vera after water exposure a significantly increased AChE activity suggesting acetylcholine release was observed, whereas in the patient with cold urticaria and the controls, a significant decrease was noted [12].
• We report a rare case of eosinophilic leukemia transformation in a patient with polycythemia rubra vera on hydroxycarbamide (hydroxyurea) therapy only [13].

Biological context of CD177

• CD177 polymorphisms: correlation between high-frequency single nucleotide polymorphisms and neutrophil surface protein expression [14].
• Neutrophil-specific antigen HNA-2a (NB1, CD177): serology, biochemistry, and molecular biology [15].
• Newly characterized markers, such as altered expression of polycythemia rubra vera-1 (PRV-1) and the thrombopoietin receptor (c-MPL) as well as deletions on chromosome 20q (del20q) and loss of heterozygosity on chromosome 9p (9pLOH) provide an opportunity to diagnose and identify subpopulations of MPD patients [16].
• Experiments show that the expression of mPR3 and CD177 on the plasma membrane is increased or decreased in parallel during cell stimulation or spontaneous apoptosis [17].
• Changes in CD177 expression may be a marker of increased or decreased myelopoiesis and are therefore an effect of, rather than a cause of, myeloproliferative disorders [18].

Anatomical context of CD177

• The size of the neutrophil population in each donor that stained brightly with CD177 antibody was assessed by flow cytometry [14].
• Furthermore, we observed a rapid internalization and recirculation of mPR3 and plasma membrane CD177, where all mPR3 is replaced within 30 min [17].
• PR3- and CD177-expressing neutrophils constitute a subpopulation of neutrophils with an unknown role in the innate immune system, which may play an important role in diseases such as Wegener's granulomatosis and polycythemia vera [17].
• Neutrophils isolated from the bone marrow, or from peripheral blood following granulocyte colony-stimulating factor administration showed markedly higher CD177 expression than circulating granulocytes on steady state [19].
• COS-7 cells transfected with the cDNA expressed immunoreactive NB1 glycoprotein [9].

Associations of CD177 with chemical compounds

• HNA-2 antigens are located on 58- to 64-Kd glycoprotein, CD177, and are encoded by a gene on chromosome 19 that belongs to the Ly-6 family [20].
• PRV-1 is a member of the uPAR/CD59/Ly6 family of cell surface receptors, which share a common cysteine-rich domain and are tethered to the cell surface via a glycosylphosphatidylinositol (GPI) link [21].
• When neutrophils were stimulated with C5a, PMA, or FMLP, no differences were found in the adhesion of NB1-positive and NB1-negative cells to the same surfaces [22].
• A patient with polycythemia rubra vera had had a leukocyte count between 55,000 and 86,000/cu mm and had had serum glucose levels as low as 8 mg/dL [23].
• Surface expression of the NB1 antigen was slightly up-regulated by treatment with the chemotactic peptide f-met-leu-phe [24].

Regulatory relationships of CD177

• A JAK2 inhibitor eliminated the V617F-induced increase in PRV-1 expression [25].
• Quantitative real-time polymerase chain reaction shows that treatment with interferon reduces the initially upregulated PRV-1 expression in polycythemia vera patients [26].
• Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1 [27].

Other interactions of CD177

• The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript [28].
• Interestingly, decreased c-MPL and elevated PRV-1 also were observed in patients with hereditary thrombocythemia (HT) who carry a mutation in the thrombopoietin (TPO) gene [29].
• Decreased expression of c-MPL protein in platelets, increased expression of polycythemia rubra vera 1 (PRV-1) and nuclear factor I-B (NFIB) mRNA in granulocytes, and loss of heterozygosity on chromosome 9p (9pLOH) were described as molecular markers for myeloproliferative disorders (MPDs) [29].
• Patients with PV who were homozygous or heterozygous for JAK2-V617F exhibited higher levels of expression of the 13 new markers, PRV1, and NF-E2 than patients without JAK2-V617F, whereas ANKRD15 was down-regulated in these patients [30].
• The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO [28].

Analytical, diagnostic and therapeutic context of CD177

• Assessment of the relative number of copies of the gene encoding human neutrophil antigen-2a(HNA-2a), CD177, and a homologous pseudogene by quantitative real-time PCR [31].
• In this study, we have investigated the molecular basis of the heterogeneous expression of NB1 GP by separating the 2 neutrophil subpopulations using immunofluorescence followed by single-cell picking or by fluorescence-activated cell sorter [32].
• Northern blot analysis detects multiple PRV-1 transcripts [21].
• Fluorescence in situ hybridization analysis of the PRV-1 gene in polycythemia vera: implications for its role in diagnosis and pathogenesis [33].
• Among these, RT-PCR is the most rapid, reliable, and feasible method for the detection of PRV-1 overexpression in highly purified peripheral blood granulocytes [34].

References