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)

N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) was administered p.o. to 199 patients with acute leukemia, myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD). Of 76 patients with AML, 11 achieved complete remission (CR) and 7 achieved partial remission (PR). Of 8 patients with ALL, 2 achieved CR and 1 achieved PR. Of 3 patients with blast crisis of MPD, 1 achieved CR. CR was reached with PL-AC at 100-900 mg/day after 5-98 (median 26) days. Of 50 patients with MDS, 2 achieved CR, 2 showed good response and 7 partial response. Response was reached with 100-400 mg/day after 13-122 (median 32) days. Improvement of polycythemia vera was observed in 6 of 13 patients, and reduction of thrombocytosis was observed in 20 of 23 patients with essential thrombocythemia and myelofibrosis. Of 18 patients with CML, 1 achieved CR. Major side effects were GI toxicities and myelosuppression. In spite of the disadvantages of the oral form of the drug, such as unpredictable absorption, PL-AC may be useful in the treatment of acute leukemia, especially that of the aged, a condition for which intensive chemotherapy is not always indicated, and MDS, which do not necessarily require admission to a hospital.
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PMID:[A phase II study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) in patients with acute leukemia and myelodysplastic syndromes. Cooperative Study Group for PL-AC]. 361 59

During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25-70 x 10(6) units/week; maintenance therapy following week 8 of treatment consisted of 20-35 x 10(6) units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440 x 10(9)/l and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.
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PMID:Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders. 367 27

N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was administered PO to 76 patients with acute leukemia, myelodysplastic syndromes (MDSs), and myeloproliferative disorders (MPDs). Of 20 patients with acute myelogenous leukemia, 2 achieved complete remission, and the only patient with acute lymphoblastic leukemia achieved partial remission. Remission was reached with PLAC 100-300 mg/day 25-66 days after the start of therapy. Among 22 patients with MDS, 1 patient achieved a good response and 8 achieved partial response. Responses were reached with PLAC 50-200 mg/day 7-153 days (median, 33 days) after the start of therapy. Improvement of polycythemia was observed in all 5 patients with polycythemia vera, and reduction of thrombocytosis was observed in 5 out of 6 patients with essential thrombocythemia and myelofibrosis. An antileukemia effect was noted in 1 of 5 with chronic myelogenous leukemia. Major side effects were gastrointestinal toxicities and myelosuppression. In spite of the disadvantages, such as unpredictable absorption and a lower response rate to acute leukemia compared with its parent compound, this antileukemia Ara-C analogue that is administrable PO will be useful in the treatment of MDSs and MPDs, which do not necessarily require admission to hospital, and in the treatment of acute leukemia of the aged, a condition for which intensive chemotherapy is not appropriate.
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PMID:Treatment of leukemia and myelodysplastic syndromes with orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine. 371 96

Based on the previous finding that erythrocytes from patients with chronic myelogenous leukemia stain with the fluorescent dye merocyanine 540, erythrocytes from patients with other myeloproliferative disorders were examined for their ability to bind the membrane probe. As assessed by both fluorescence staining and a quantitative dye removal assay, all samples of erythrocytes from patients with chronic myelogenous leukemia, polycythemia vera, myelofibrosis with myeloid metaplasia and essential thrombocythemia bound more dye than did erythrocytes from normal, healthy individuals. Erythrocytes from three of six patients with acute myelogenous leukemia also showed increased affinity for the dye. In contrast, erythrocytes from three patients with acute lymphocytic leukemia and one with unclassifiable leukemia bound only normal amounts of dye. The procedures described may be useful as a supplemental aid to diagnosis of myeloproliferative disorders or for investigation of hematological diseases where multilineage involvement is suspected.
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PMID:A fluorescent dye which recognizes mature peripheral erythrocytes of myeloproliferative disorders. 382 30

Sixty-seven patients with hematological malignancies and 4 with cancers were evaluated in this study. Standard administration of MCNU was instituted intravenously using 50-100 mg/m2 every 2 or 4 weeks, whereas some cases were treated with a higher dose therapy. Of 10 patients with chronic myelogenous leukemia, 7 achieved complete remission (CR), and 1 achieved partial remission (PR). A good response was also obtained in 9 of 10 patients with polycythemia vera and in all 4 patients with essential thrombocythemia. MCNU was less effective in malignant lymphoma (ML) and multiple myeloma (MM) than in myeloproliferative disorders. Two of 15 patients with ML and one of 21 patients with MM achieved CR, and two with ML and three MM achieved PR. Three patients with lung cancer and 1 with gastric cancer showed no response to MCNU. Delayed anemia, leukocytopenia and thrombocytopenia were observed in 38.7% of patients, and these were regarded as major side effects of MCNU. Nausea, vomiting, anorexia and elevated transaminase were also found in about 24% of patients, but only transiently. Our study indicates that MCNU is useful for chemotherapy of hematological malignancies, especially of myeloproliferative disorders. Therefore, further studies on combination chemotherapy with MCNU should be developed.
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PMID:[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)]. 385 48

Previous studies with the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) as a marker of cellular mosaicism demonstrated that polycythemia vera (PV) and essential thrombocythemia (ET) are clonal disorders of hematopoietic stem cells that can differentiate to erythrocytes, granulocytes, and platelets. To determine if the involved stem cells could also differentiate along the B-lymphoid pathway, we studied one woman with PV and one woman with ET. Of 117 Epstein-Barr virus-transformed B-lymphoblastoid lines expressing a single G6PD derived from the patient with PV, 108 expressed G6PD type A, the type characteristic of the abnormal clone. The ratio of 108:9 was significantly different from the one to one ratio predicted for this patient, which suggested that at least some circulating progenitors for B-lymphoid cell lines differentiate from the stem cell involved by the disease. Results obtained from the patient with ET were similar--104 of the 109 lymphoblastoid lines monotypic for G6PD expression displayed the enzyme type found in the abnormal clone of marrow cells. Therefore, in these patients, PV and ET, like chronic myelogenous leukemia, involve a stem cell pluripotent for the lymphoid as well as the myeloid series.
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PMID:Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia. 392 71

The progression of primary thrombocythemia (PT) into acute leukemia was diagnosed in a 64-year-old man who was previously treated by hydroxyurea without alkylating agents or radioactive phosphorus. Such an event has only been reported in very rare cases. The blast cells had a lymphocytic morphology but were identified as promegakaryoblasts by the ultrastructural demonstration of platelet peroxidase. These data suggest that a megakaryoblastic transformation could occur in PT as had previously been reported in chronic granulocytic leukemia.
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PMID:Megakaryoblastic transformation of primary thrombocythemia. 393 45

An obligately anaerobic, gram-negative microorganism identified as a Sphaerophorus species was recovered from the fecal material of two cancer (chronic myelogenous leukemia and idiopathic thrombocythemia) patients receiving cobalt radiation therapy. The organism, isolated on sheep blood-agar, exhibited extreme pleomorphism (rods, filaments, and spheroids) and was a major component of the anaerobic fecal microflora. In one patient the numbers of Sphaerophorus species (designated as isolate 6-13-68), Bacteroides species, and Clostridium perfringens declined after irradiation; however, they were stable in this same patient after a second therapeutic dose of radiation. The numbers of anaerobes in the other patient remained fairly consistent after radiation. The biochemical and morphological characteristics and carbohydrate fermentation reactions of isolate 6-13-68 most closely resembled those of Sphaerophorus ridiculosis.
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PMID:Unusual Sphaerophorus species from the large intestine of man. 431 40

Abnormal proliferation of the megakaryocytic line was observed in the marrow tissue from patients with myeloproliferative disorders. Megakaryocytes were identified by immunofluorescence using distinct platelet protein markers. Plasma factor VIII antigen (factor VIII:AGN) and platelet glycoproteins IIb and IIIa were detected in normal mature and early megakaryocytes, as well as in a morphologically heterogeneous population of low density marrow cells regarded as atypical megakaryocytes. Atypical megakaryocytes were defined as oval/round 14-35-micron diameter blast-like mononuclear/multinucleated cells bearing platelet protein markers with distinct morphological features, including cytoplasmic vacuolation, variable nuclear/cytoplasmic ratios, and variable cytoplasmic granulation. Atypical megakaryocytes were observed in most chronic myelogenous leukemia (CML) patients and in two patients with polycythemia vera, representing between 60 and 1,840 cells/10(4) cells (less than 1.050 g Percoll/cu cm). No atypical megakaryocytes were found in (a) 20 normal controls, (b) two patients with essential thrombocythemia, (c) a patient with thrombocytosis secondary to acute bleeding, and (d) in two patients with CML. Atypical megakaryocytes appear to represent a single-cell population, as demonstrated by a series of double immunofluorescence assays using combinations of five different antiplatelet protein sera. There was a statistically significant correlation between the frequency of atypical megakaryocytes and the presence of immature forms of myeloid cells in blood. Analyses of Fc IgG receptors conducted with two different immunofluorescence systems have demonstrated that phenotypic similarities existed between atypical megakaryocytes and myeloproliferative platelet proteins and differentiation markers on megakaryocytes are useful in elucidating the pathophysiologic alterations occurring in the megakaryocytic compartment in patients with myeloproliferative disorders.
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PMID:Human megakaryocytes. III. Characterization in myeloproliferative disorders. 623 Jan 21

The arachidonate metabolism by leukocytes and platelets was studied in 14 patients with myeloproliferative disorders including 7 patients with chronic myeloid leukemia (CML), 5 with polycythemia vera (PV) and 2 with essential thrombocythemia (ET). When the leukocytes were incubated with arachidonate and A23187, leukotriene B4 and hydroxyeicosatetraenoic acids (HETEs) were constantly detected using reversed-phase high-performance liquid chromatography in normal subjects, while selective deficiency of 5-lipoxygenase products (leukotriene B4 and 5-HETE) was found in 4 patients with CML. this novel abnormality of the leukocytes seemed to be derived from the possible deficiency of 5-lipoxygenase in these patients' polymorphonuclear neutrophils (PMNNs). The formation of 15-HETE appeared to be almost normal in all the patients. Platelet 12-lipoxygenase deficiency was detected in 2 patients with PV and 2 with CML in whom one was associated with the deficiency of 5-lipoxygenase products. These bicellular abnormalities of the arachidonate metabolism might contribute to understand dysfunctions of PMNNs and platelets in some patients with myeloproliferative disorders.
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PMID:Altered arachidonate metabolism by leukocytes and platelets in myeloproliferative disorders. 631 27


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