Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with polycythemia vera (PV) have a JAK2 (a cytosolic tyrosine kinase) mutation and an increased risk of vascular thrombosis related to red blood cell (RBC) mass and platelet activation. We investigated functional RBC abnormalities that could be involved in thrombosis. RBC adhesion to human umbilical vein endothelial cells (HUVECs) was measured by a radiometric technique and in a flow system by video microscopy, and adhesion molecule expression was determined using specific antibodies (against CD36, CD49d, ICAM-4, Lu/BCAM, CD147, and CD47) and flow cytometry in a group of 38 patients with PV and a group of 36 healthy volunteers. Adhesion of PV RBCs was 3.7-fold higher than that of normal RBCs (P < .001). Adhesion was inhibited when PV RBCs were incubated with anti-Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) or when HUVECs were treated with anti-laminin alpha(5) and to a lesser extent with anti-alpha(3) integrin. Lu/BCAM was constitutively phosphorylated in PV RBCs. Transfection of K562 cells with JAK2 617V>F resulted in increased expression and phosphorylation of Lu/BCAM. Phosphorylation of Lu/BCAM increases RBC adhesion. Our results indicate that JAK2 mutation might be linked to Lu/BCAM modification and increased RBC adhesiveness, which may be a factor favoring thrombosis in PV.
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PMID:Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin alpha5 chain and Lu/BCAM. 1741 90

The Lutheran blood group system consists of 19 antigens: four pairs of antithetical antigens--Lu(a)/Lu(b), Lu6/Lu9, Lu8/Lu14, and Au(a)/Au(b)--and 11 antigens of very high frequency. These antigens are located on four of the five immunoglobulin-like domains of both isoforms of the Lutheran glycoprotein. The LU gene is on chromosome 19 and comprises 15 exons. The two glycoprotein isoforms differ in the length of their cytoplasmic tails as a result of alternative splicing of intron 13. Lu(null) phenotype arises from homozygosity for inactivating mutations in the LU gene.The dominantly inherited Lu(mod) phenotype, In(Lu), results from heterozygosity for inactivating mutations in KLF1, the gene for the erythroid transcription binding factor EKLF. Clinically, antibodies of the Lutheran system are relatively benign. When hemolytic, they generally cause only mild, delayed hemolytic transfusion reactions or hemolytic disease of the fetus and newborn that can be treated by phototherapy. The Lutheran glycoproteins, which are members of the immunoglobulin superfamily of adhesion molecules and receptors, bind isoforms of laminin with alpha5 chains,components of the extracellular matrix abundant in vascular endothelia. The primary function of the Lutheran glycoproteins on RBCs could involve the transfer of maturing RBCs from the bone marrow to the peripheral circulation. They could also be involved in vascular occlusion and thrombotic events as complications of sickle cell disease and polycythemia vera, respectively.
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PMID:Lutheran. 2040 22

The extent of red blood cell adhesion is correlated with the incidence of vascular complications and the severity of the disease. Patients with sickle cell anemia (HbSS) experience vasoocclusive episodes. The adhesion of RBCs from HbSS patients is increased and related to VLA-4 exposure, which binds to vascular cell adhesion molecule (VCAM-1). Inter Cellular Adhesion Molecule (ICAM-1), CD31, CD36 and glycans are potential receptors for PfEMP1 of RBCs parasited by plasmodium falciparum. The incidence of vascular complications is very high in patients with diabetes mellitus. RBC adhesion is increased and statistically correlated with the severity of the angiopathy. Glycation of RBC membrane proteins is responsible for binding to the receptor for advanced glycation end products (RAGE). Polycythemia Vera (PV) is the most frequent myeloproliferative disorder and characterized by a high occurrence of thrombosis of mesenteric and cerebral vessels. PV is due to a mutation of the Janus kinase 2 (JAK2 V617F). This mutation stimulates erythropoiesis and is the cause of Lu/BCAM (CD239) phosphorylation, which potentiated the interaction with laminin alpha 5. The couple laminin alpha 5 endothelial and phosphorylated Lu/BCAM explained the increased adhesion of RBCs from patients PV to endothelium.
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PMID:[Molecular basis of red blood cell adhesion to endothelium]. 2129 12