Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin (PG) D(2) is synthesized in platelets at concentrations which could inhibit aggregation via activation of adenylate cyclase. To more directly define platelet-PG interactions, a binding assay has been developed for platelet PG receptors with [(3)H]PGD(2) as ligand. [(3)H]PGD(2) binding to intact platelets was saturable and rapid with the ligand bound by 3 min at 20 degrees C. PG competed with the [(3)H]PGD(2) binding site with a potency series: PGD(2) (IC(50) = 0.08 muM) >> PGI(2) (IC(50) = 2 muM) > PGE(1) (IC(50) = 6 muM) > PGF(2alpha) (IC(50) = 8 muM). Scatchard analysis of binding data from six normal subjects showed a single class of binding sites with a dissociation constant (K(d)) of 53 nM and 210 binding sites per platelet. This PGD(2) receptor assay was then used to study platelets from five patients with myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and chronic myelogenous leukemia), as over 90% of these patients have platelets resistant to the effects of PGD(2) on aggregation and adenylate cyclase activity (1978. Blood.52: 618-626.). In the presence of 50 nM [(3)H]PGD(2), the patients' platelets bound 7.1+/-2.9 fmol ligand/10(8) platelets compared with 15.1+/-1 fmol/10(8) platelets in normals, a decrease of 53% (P < 0.01). Scatchard analysis showed that the K(d) of [(3)H]PGD(2) binding (33 nM) was comparable to normal platelets, which indicates that the decreased PGD(2) binding in these platelets represented fewer receptors rather than altered affinity of the ligand for the binding site. The 53% decrease in [(3)H]PGD(2) binding correlated with a 48% decrease in PGD(2)-activated platelet adenylate cyclase. The characterization of the platelet PGD(2) binding site provides further direct evidence that there are at least two PG receptors on platelets, one for PGE(1) and PGI(2), and a separate receptor for PGD(2). Direct binding analysis will be a useful tool for studying the role of PG in regulating platelet function, as demonstrated by the selective loss of PGD(2) binding sites in patients with myeloproliferative disorders.
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PMID:Characterization of the platelet prostaglandin D2 receptor. Loss of prostaglandin D2 receptors in platelets of patients with myeloproliferative disorders. 22 13

The authors investigated the behaviour of steroid hormone uptake in leukaemic cells (CML, CLL, AML, ALL), in basal conditions and after incubation with drugs which modify the cellular concentration of cAMP, PGE and PGF. The results demonstrated the presence in leukaemic cells of an alteration in the incorporation of steroid hormones. This alteration was scarcely modified by incubation with theophylline, which increases cellular concentration of cAMP. On the other hand, it was moderately counteracted by thioproline and was evidently inhibited by flurbiprofen, which also reduced cellular concentrations of prostaglandins, particularly PGE2, with the exception of PGF2 which showed a poor response. Differences were observed in the behavior of hormonal uptake of CML, in contrast to that of AML, CLL and ALL peripheral leucocytes.
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PMID:Drugs affecting the hormonal receptors of normal and leukaemic peripheral leucocytes. 651 20

Prostaglandins of the E series (PGE) have varying effects in vitro on normal granulocyte/macrophage (CFU-GM) progenitors. When added directly to cultures, PGE inhibits growth of normal 7 and 14 day bone marrow CFU-GM in a dose-dependent manner, while CML CFU-GM are refractory to PGE inhibition. The plant diterpene forskalin, a potent activator of intracellular cyclic AMP, inhibited normal and CML CFU-GM, indicating that the response of CML cells to increased intracellular cyclic AMP is normal. Low dose forskalin, which potentiates activators of adenyl cyclase, showed additive effects with PGE on normal CFU-GM cells, however, showed no additive effects of PGE and forskalin, suggesting that PGE failed to activate adenyl cyclase. Normal CFU-GM incubated with PGE for two hours showed a significant increase in CFU-GM growth, and removal of adherent cells prior to exposure to PGE abrogated this effect. CML cells did not respond to a 2-h exposure to PGE, and removal of adherent cells from these cultures had no effect. Normal and CML CFU-GM showed dose-dependent increases in proliferation in the presence of PGF2. These studies confirm that CML CFC-GM are refractory to inhibition by PGE, and show that these cells respond normally to increased levels of intracellular cyclic AMP. Response of CML cells to PGF2 alpha is normal, and conversion of PGE to PGF could result in increased granulocyte progenitor proliferation.
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PMID:Further studies on mechanisms of abnormal prostaglandin response by chronic myelogenous leukaemia granulocyte/macrophage progenitors. 659 11

The behaviour of prostaglandins A, B, E 1, E 2, F 1 and F 2 has been examined in the granulocytes and lymphocytes of the peripheral blood of normal subjects and in circulating leucocytes of patients with CML, AML, CLL and ALL. At the same time, modifications of PGE 2 in the granulocytes of normal subjects and in patients with CML or AML before and after phagocytosis of latex particles were monitored. The general observation was a lowering in PGE and PGF in acute myeloid and lymphatic leukaemia, while the variations in CML and CLL were rather complex. Also observed was a reduction in PGE 2 in AML but not in CML, including a reduced response to phagocytosis in granulocytes. The data are compared with previous reports of AMPc and GMPc in the same cells and commented on, taking into consideration their possible reflexion on the proliferative and functional activity of the cells examined.
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PMID:[Behavior of several prostaglandins (PGA, PGB, PGE 1, PGE 2, PGF 1, PGF 2) in normal and leukemic leukocytes. Radioimmunological method on intact cells]. 724 9