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)

Erythrocytes were hemolyzed in hypotonic phospate buffer containing 0.5 mmol/l Ca2+ and the membranes subsequently washed twice in hypotonic tris buffer. The centrifugation was performed in a continuous flow system, which was necessary to obtain maximal ATPase activity. The Mg2+-dependent Ca2+-stimulated ATPase activity of 14 patients with polycythemia vera was only 67 per cent (P less than 0.001) of the activity of a control material consisting of 10 donors and 11 bank blood specimens. Five patients with secondary polycythemia and four patients with an increased erythrocyte fraction did not differ significantly from the controls. The polycythemia vera patients with the highest leukocyte count showed the lowest ATPase activity. The apparent calcium dissociation constant of the ATPase in polycythemia vera was about 10(-6) mol/l, as in controls. The relation between the reduced ATPase activity and the abnormal hemopoiesis of polycythemia vera patients is discussed.
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PMID:Decreased (Ca2+ + Mg2+)-stimulated ATPase activity in erythrocyte membranes from polycythemia vera patients. 12 20

The JAK2(V617F) mutation is frequently observed in classical myeloproliferative disorders, and disease progression is associated with a biallelic acquisition of the mutation occurring by mitotic recombination. In this study, we examined whether JAK2 activation could lead to increased homologous recombination (HR) and genetic instability. In a Ba/F3 cell line expressing the erythropoietin (EPO) receptor, mutant JAK2(V617F) and, to a lesser extent, wild-type (wt) JAK2 induced an increase in HR activity in the presence of EPO without modifying nonhomologous end-joining efficiency. Moreover, a marked augmentation in HR activity was found in CD34(+)-derived cells isolated from patients with polycythemia vera or primitive myelofibrosis compared with control samples. This increase was associated with a spontaneous RAD51 foci formation. As a result, sister chromatid exchange was 50% augmented in JAK2(V617F) Ba/F3 cells compared with JAK2wt cells. Moreover, JAK2 activation increased centrosome and ploidy abnormalities. Finally, in JAK2(V617F) Ba/F3 cells, we found a 100-fold and 10-fold increase in mutagenesis at the HPRT and Na/K ATPase loci, respectively. Together, this work highlights a new molecular mechanism for HR regulation mediated by JAK2 and more efficiently by JAK2(V617F). Our study might provide some keys to understand how a single mutation can give rise to different pathologies.
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PMID:JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders. 1851 59