Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To address a possible impairment of multidrug resistance mechanisms in acquired aplastic anaemia (AA), the functions of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) were respectively assessed by rhodamine 123 (Rh123) and daunorubicin (DNR) efflux in peripheral blood lymphocytes from AA patients. The proportion of Rh123-effluxing T cells was significantly decreased in AA, relative to controls. Interestingly, these changes were also present in patients with AA in remission. Conversely, Rh123 efflux in B and natural killer (NK) cells and DNR efflux in peripheral blood lymphocytes were unchanged. These data indicated that P-gp activity was decreased in AA not only during the development of the disease, but also after remission, introducing a new concept on the pathophysiology of AA by suggesting that it may contribute to drug-induced injury to haemopoietic cells in some cases of AA, by increasing the proportion of susceptible cells.
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PMID:Decreased activity of the multidrug resistance P-glycoprotein in acquired aplastic anaemia: possible pathophysiologic implications. 975 37

We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.
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PMID:Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome. 1137 33

Drug exposure is implicated in the aetiology of some cases of acquired aplastic anaemia (AA), but the reason for this susceptibility remains unclear. We previously demonstrated that P-glycoprotein (P-gp) function, a drug efflux pump, is decreased in AA lymphocytes. To further evaluate whether P-gp activity is also abnormal in AA stem cells, we examined bone marrow (BM) CD34+ cells from newly diagnosed AA patients (AA-d, n = 25), after immunosuppression (AA-IST, n = 13) and after BM transplantation (AA-BMT, n = 8). Of the AA patients with autologous haematopoiesis (AA-d + AA-IST), 15 had drug-induced AA. Thirty-two BM donors were studied as controls. P-glycoprotein function was assessed by the rhodamine 123-efflux assay. P-glycoprotein function in CD34+ cells was reduced in AA-d patients (17.8%, 0-67.7) compared with controls (42.5%, 13.4-57.4; P < 0.001), as well as in AA-IST (20.3%, 1.2-32.0; P < 0.001), but not in AA-BMT (40.9%, 19.0-55.9). P-gp function was reduced more in drug-induced AA (14.5%, 0-27.4) than in the other cases (26.1%, 0-67.7; P = 0.04), but it did not correlate with disease severity. These results indicate that P-gp function is defective in AA CD34+ cells, pointing to a role of P-gp in increased cell susceptibility to xenobiotics in AA.
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PMID:Reduced function of the multidrug resistance P-glycoprotein in CD34+ cells of patients with aplastic anaemia. 1210 Jan 68

Aplastic anemia is a rare complication of allopurinol use. We report an unusual case of aplastic anemia associated with allopurinol therapy for hyperuricemia in a patient with chronic kidney disease. A 37-year-old female patient diagnosed with Stage III chronic kidney disease was admitted with pancytopenia. She had a history of taking allopurinol for 5 months. Her bone marrow showed extremely decreased cellularity (< 20%) and there was no malignant cell infiltration. She was free of infections, including parvovirus B19, cytomegalovirus and Epstein-Barr virus. These results suggested a diagnosis of aplastic anemia. Allopurinol was discontinued immediately and treatment with blood transfusions and prednisolone was begun. After 6 months, the bone marrow cellularity improved to approximately 70%. Recently, it was suggested that decreased activity of multidrug resistance P-glycoprotein may play a role in acquired aplastic anemia. So we measured the inhibitory effect of allopurinol and oxypurinol on P-glycoprotein activity. But neither allopurinol nor oxypurinol inhibited P-glycoprotein activity.
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PMID:Allopurinol-induced aplastic anemia in a patient with chronic kidney disease. 1920 17