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)

Abnormalities in platelet dense granules, small intracellular organelles containing ATP, ADP, calcium, serotonin, and pyrophosphate, have frequently been reported in patients with leukemia and myeloproliferative disorders, particularly acute and chronic myelogenous leukemia. Recent studies of a family which includes several members with an autosomal dominant dense granule deficiency condition show an association between the presence of this form of dense granule deficiency and the development of acute myelogenous leukemia. Studies in two additional patients, one with the Monosomy 7 syndrome and the second with a myelodysplastic syndrome, revealed a defect in platelet dense granules. This defect appears to be due to an abnormality in the formation of these granules rather than the presence of empty vesicular structures or decreased contents due to activation associated secretion. The results suggest that the defect in platelet dense granules associated with leukemia or myelodysplastic syndromes may result from a chromosome alteration in the megakaryocyte cell line leading to decreased formation of dense granules. Studies in the family with an inherited bleeding disorder suggest that a gene coding for a protein important for the formation of dense granules is located adjacent to a gene which, when abnormal, may predispose to the development of leukemia.
 ...
PMID:Platelet storage pool deficiency, leukemia, and myelodysplastic syndromes. 129 Sep 57

Bleeding time, clot retraction, platelet factor 3 availability and platelet aggregation in response to ADP, epinephrine, collagen and ristocetin were studied in 12 cases of chronic leukemia which included eight of chronic myeloid leukemia, two of chronic lymphatic leukemia and two of CLL related disorders. One or more abnormalities in platelet function were detected in all the cases. Among the cases of CML, bleeding time was prolonged in one, clot retraction was impaired in one and PF3 availability was decreased in one case. Defects in platelet aggregation were variable. Among the cases of CLL and CLL related disorders, bleeding time was prolonged in two, clot retraction was impaired in one and PF3 availability was decreased in three cases. Platelet aggregation responses were significantly impaired in all the cases.
 ...
PMID:Platelet function in chronic leukemias. 147 32

The content of adenine nucleotides (ATP, ADP) was studied in dense granules of platelets in hemoblastosis to estimate the character of the pathological process course. Varying biochemical defects were observed at the levels of ATP and ADP depending on the severity of the pathological process in chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloblastic and acute myelo-monoblastic leukemias. Adenine nucleotide values can be used for the diagnosis of varying stages of the above diseases, for the evaluation of anomalous platelets and characterization of the adequacy of the bone marrow hemopoiesis.
 ...
PMID:[Assay of adenine nucleotide level in platelet storage pool for evaluation of the course of hemoblastosis]. 147 25

2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-adenine (Cl-F-ara-A) has activity against the P388 tumor in mice on several different schedules. Biochemical studies with a chronic myelogenous leukemia cell line (K562) grown in cell culture have been done in order to better understand its mechanism of action. Cl-F-ara-A was a potent inhibitor of K562 cell growth. Only 5 nM inhibited K562 cell growth by 50% after 72 h of continuous incubation. The 5'-triphosphate of Cl-F-ara-A was detected by strong anion exchange chromatography of the acid-soluble extract of K562 cells incubated with Cl-F-ara-A. Competition studies with natural nucleosides suggested that deoxycytidine kinase was the enzyme responsible for the metabolism to the monophosphate. Incubation of K562 cells for 4 h with 50 nM Cl-F-ara-A inhibited the incorporation of [3H]thymidine into the DNA by 50%. Incubation with 0.1, 1, or 10 microM Cl-F-ara-A for 4 h depressed dATP, dCTP, and dGTP pools but did not affect TTP pools. Similar inhibition of deoxyribonucleoside triphosphate pools was seen after incubation with 2-chloro-2'-deoxyadenosine. Both Cl-F-ara-ATP and Cl-dATP potently inhibited the reduction of ADP to dADP in crude extracts of K562 cells (concentration producing 50% inhibition, 65 nM). The effect of Cl-F-ara-ATP on human DNA polymerases alpha, beta, and gamma isolated from K562 cells grown in culture was determined and compared with those of Cl-dATP and 9-beta-D-arabinofuranosyl-2-fluoroadenine triphosphate (F-ara-ATP). Cl-F-ara-ATP was a potent inhibitor of DNA polymerase alpha. Inhibition of DNA polymerase alpha was competitive with respect to dATP (Ki of 1 microM). The three analogue triphosphates were incorporated into the DNA by DNA polymerase alpha as efficiently as dATP. The incorporation of Cl-F-ara-AMP inhibited the further elongation of the DNA chain, similarly to that seen after the incorporation of F-ara-AMP. Extension of the DNA chain after the incorporation of Cl-dAMP was not inhibited as much as it was with either Cl-F-ara-AMP or F-ara-AMP. Cl-F-ara-ATP was not a potent inhibitor of DNA polymerase beta, DNA polymerase gamma, or DNA primase.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5'-triphosphate. 170 52

Platelet activation in patients with myeloproliferative disorders is often suggested by increased platelet alpha-granule secretion and an acquired storage pool defect of dense granules. To determine whether activated platelets circulate in patients with chronic myeloproliferative disorders, we evaluated the binding of monoclonal antibodies against activation-dependent epitopes on resting platelets (P 12, CD 63, and CD 62) in 12 patients with prominent megakaryocytic proliferation (8 patients with essential thrombocythemia, 2 with chronic myeloid leukemia, and 2 patients with polycythemia rubra vera). In addition, platelet aggregation in response to collagen, adenosine diphosphate, platelet activating factor, and agglutination with ristocetin was investigated. In 3 patients there was an increased percentage of platelets binding at least 1 activation marker. In 2 other patients, a trend towards increased antibody binding was observed. Binding of the antibody to thrombospondin (P 12) was related to expression of the GMP 140 protein (CD 62, r = 0.76, p = 0.004). There was no correlation of platelet aggregation defects in vitro to increased expression of platelet activation markers or to thrombohaemorrhagic complications. However, circulating activated platelets were detected in three out of five patients with a history of bleeding or thrombotic complications. The results of this preliminary study suggest that some but not all patients with myeloproliferative disorders showed increased amounts of circulating activated platelets. The relation of bleeding and thrombotic complications to the expression of activation-dependent epitopes on platelets in myeloproliferative disorders requires further investigation.
 ...
PMID:Circulating activated platelets in myeloproliferative disorders. 170 9

Platelet functions and morphological changes of megakaryocytes were investigated in three cases with chronic neutrophilic leukemia (CNL). The bleeding time was prolonged, the ADP, collagen, epinephrine-induced aggregation of platelets decreased in one case. The adhesiveness, epinephrine-induced aggregation and adenine nucleotide content of platelets decreased in one other case. Megakaryocyte size in CNL was larger than in CML and this difference of the megakaryocyte sizes was related to DNA content distribution of the megakaryocytes. Atypical megakaryocytes were apparently found in one case. The present study suggests that CNL is a stem cell disorder.
 ...
PMID:[Changes in the megakaryocyte-platelet system in chronic neutrophilic leukemia]. 177 59

Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase. This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and mezerein produced an increase in poly ADPRT activity in both normal and CML lymphocytes, but the increase was more marked in the case of normals. This was accompanied by a drop in NAD levels. The results presented show a marked increase in poly ADP-ribosylation in malignant cells but normal lymphocytes showed a greater response to tumour promoters as compared to CML lymphocytes.
 ...
PMID:Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers. 190 97

The content of platelet adenine nucleotide in chronic myeloproliferative disorders (CMPD) and multiple myeloma (MM) was measured by a luciferin-luciferase method by Holmsen and Weiss. The release of ATP and ADP from platelet during aggregation induced by collagen and epinephrine were analyzed. The total 42 investigated cases consisted of 11 cases of polycythemia vera (PV), 7 cases of essential thrombocythemia (ET), 7 cases of chronic myeloid leukemia (CML), 9 cases of blastic crisis of CML (BC-CML), and 8 cases of multiple myeloma (MM). The healthy control was 19 cases. In CMPD and MM, the amount of ATP was normal in spite of decrease of ADP; therefore, the ratio of ATP/ADP increased. On the other hand, the ATP significantly increased in BC-CML. MM revealed a remarkable increase of ATP release due to the aggregation by collagen and epinephrine. The maximal rate of aggregation of collagen and epinephrine using Lumi-aggregometer indicated a positive relationship with the ATP release by the Holmsen and Weiss' method. The platelet volume in CMPD increased showing correlation with ATP content and not with ADP. In conclusion, CMPD and MM are regarded as acquired qualitative disorders of platelets or secondary storage pool diseases from the view points of the abnormalities in ATP, ADP contents and their release. However, BC-CML and MM revealed some different change from that of CMPD.
 ...
PMID:[ATP and ADP of platelets in chronic myeloproliferative disorders and multiple myeloma]. 271 95

The new Cobe CML membrane oxygenator is more compact than other membrane oxygenators and has a combined venous and cardiotomy suction reservoir. Its size makes it as easy to use as a bubble oxygenator. The studies reported here were designed to show whether the excellent haemocompatibility found with other types of membrane oxygenators had ben compromised by the changes introduced in the Cobe CML oxygenator. Platelet number and function (ADP induced aggregation) plasma betathromboglobulin concentration and plasma haemoglobulin concentration were studied in nine patients where the Cobe CML oxygenator had been used and these were compared with ten patients managed with a Shiley S-100 bubble oxygenator. We conclude that the constructional changes of the Cobe CML oxygenator do not affect the haemocompatibility of this type of membrane oxygenator and that it remains significantly better than the Shiley S-100 bubble oxygenator.
 ...
PMID:Haematological characteristics of a new membrane oxygenator: the Cobe CML. 295 65

The thrombocytic beta-thromboglobulin (beta-TG) level--a specific globulin secreted by the alpha-granules--is an important criterion in the contemporary diagnosis of acquired thrombocytopathies. The beta-TG was determined by the radioimmunologic test of the firm "Amersham" in thrombocytic lysates and thrombocyte-poor plasma of 54 persons: 24 patients with acute leukemia, 14 patients with chronic myeloid leukemia and 15 healthy controls. The leukemic patients were with a preliminary proved thrombocytopathy type "empty thrombocytic pool disease" which had been proved via aggregation measurement by the ATP and ADP levels in the thrombocytes and by the thrombocytic factor 4 level. While the intraplatelet beta-TG concentration in acute leukemia and chronic myeloid leukemia was found unchanged, in the patients with acute leukemia its secretion in the plasma was decreased (154.71 + 16.77 ng/10(5) platelets). The data interpretation shows that in these malignant hemopathies the alpha-granules do not take part in the "empty pool disease". In acute leukemia the pathogenesis of the thrombocytopathy is determined by the so-called "thrombocytic secretion paresis" which is confirmed by the thrombocytic factor 4 low level.
 ...
PMID:[The thrombocytic beta-thromboglobulin level of patients with blastic leukemia and chronic myeloleukemia]. 297 86


1 2 3 4 5 Next >>