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

The effect of prostaglandin E1 (PGE1) on the in vitro proliferation of peripheral blood granulocyte/macrophage progenitors (CFUc) from the patients with chronic myeloproliferative disorders was examined. PGE1 was found to be a dose-dependent inhibitor of normal peripheral blood and bone marrow CFUc. Peripheral blood CFUc from patients with chronic myelogenous leukemia (CML) showed normal inhibition when cultured in the absence of exogenous colony stimulating factor (CSF). The addition of CSF to CML peripheral blood cultures resulted in complete abrogation of normal PGE1 inhibition. Dose-titration studies in which increasing amounts of CSF were added to CML cultures showed decreasing PGE1 inhibition with increasing CSF concentration. This observation indicated increased efficiency of competition between the colony stimulating effect of CSF and the colony inhibitory effect of PGE1 in CML. Peripheral blood CFUc from patients with myelofibrosis/myeloid metaplasia (MM) showed heterogeneous responses to PGE1 with complex dose-effect curves showing variable combinations of stimulation and inhibition of CFUc proliferation. Further studies showed that these effects of PGE1 were blocked by the prostaglandin antagonist SC-19220, and were not due to elaboration of CSF or non-CSF enhancers of CFUc proliferation from MM adherent cells. Cell fractionation studies in 2 patients, with MM showed dual populations of CFUc, one responding abnormally, and another normally to PGE1, accounting in part for the complex dose-response curves. These studies indicate that significant abnormalities exist in the in vitro response to PGE1 by CFUc from patients with chronic myeloproliferative disorders. Deficiencies in PGE 1 inhibition may contribute to the excess myelopoiesis seen in these disorders.
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PMID:Abnormal modulation of granulocyte/macrophage progenitor proliferation by prostaglandin E in chronic myeloproliferative disorders. 697 57

Fifty-two patients with chronic myeloproliferative disorders (13 with polycythemia vera; 23 with primary thrombocythemia; 6 with myelofibrosis and 10 with chronic granulocytic leukemia) had low platelet levels of adenine nucleotides and serotonin and abnormal uptake and storage of the amine. The storage pool deficiency was confined to the substances contained in the platelet dense bodies, because alpha-granule and lysosome markers were present in normal amounts. In chronic granulocytic leukemia the storage defect was usually less marked but was accompanied by a decreased formation of thromboxane B2 and normal platelet aggregation in response to arachidonic acid. There was no clearcut relationship of these biochemical abnormalities to prolongation of bleeding time or to thrombotic and hemorrhagic symptoms. The defect was still present in 15 patients after treatment had returned the cell counts to the normal range. Normal levels of 5HT and adenine nucleotides were observed in 8 patients whose platelet counts were high after splenectomy for non-hematological reasons. These findings suggest that biochemical abnormalities are related to the presence in the bone marrow of abnormal clones, resulting in the production of defective platelets.
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PMID:Biochemical and metabolic aspects of platelet dysfunction in chronic myeloproliferative disorders. 710 Dec 43

In order to ascertain the frequency and distribution of isochromosomes in neoplasia, we surveyed the cytogenetic data from 20,007 tumors with clonal chromosome aberrations reported in the literature. Tumor types for which at least 50 cases with acquired aberrations and 10 cases with isochromosomes had been reported were selected, yielding a total of 18,160 neoplasms. Of these, 1,792 cases (9.9%) displayed a total of 2,014 isochromosomes. The 9 most common isochromosomes (detected in at least 50 cases) were, in decreasing order of frequency, i(17q), i(8q), i(1q), i(12p), i(6p), i(7q), i(9q), i(5p), and i(21q). The frequency of isochromosomes varied among the different tumor types, with the highest incidence in germ cell neoplasms (60%) and the lowest in chronic myeloproliferative disorders (2.3%). Also, the spectrum of isochromosomes differed among the neoplasms. The most common isochromosomes in the different tumor types were i(11q), i(17q), and i(21q) in acute myeloid leukemia; i(9q), i(17q), and i(22q) in chronic myeloid leukemia; i(17q) in chronic myeloproliferative disorders; i(X)(q13), i(17q), and i(21q) in myelodysplastic syndromes; i(7q), i(9q), and i(17q) in acute lymphoblastic leukemia; i(1q), i(7q), i(8q), and i(17q) in chronic lymphoproliferative disorders; i(1q), i(6p), i(9p), i(17q), and i(21q) in Hodgkin's disease; i(1q), i(6p), and i(17q) in non-Hodgkin's lymphoma; i(1q), i(8q), and i(17q) in adenocarcinoma; i(1q), i(3q), i(5p), and i(8q) in squamous cell carcinoma; i(5p), i(8q), and i(11q) in transitional cell carcinoma; i(1q), i(7q), and i(17q) in Wilms' tumor; i(1q), i(12p), and i(17q) in germ cell neoplasms; i(1p), i(1q), i(6p), and i(17q) in sarcoma; i(5p), i(6p), i(7p), and i(21q) in mesothelioma; i(1q), i(6p), and i(17q) in malignant neurogenic neoplasms; i(1q), i(6p), and i(17q) in retinoblastoma; and i(1q), i(6p), and i(8q) in malignant melanoma.
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PMID:Isochromosomes in neoplasia. 752 35

Morphometric analysis of sections of biopsy specimens from patients with chronic myeloproliferative disorders (CMPD) can complement the individual histological diagnosis and help to distinguish the four groups of CMPD. A total of 130 diagnostic biopsies from 29 cases of chronic myelocytic leukemia (CML.CT), 26 cases of (CML.MI), 28 of essential thrombocythemia (PTH), 26 cases of chronic megakaryocytic granulocytic myelosis (CMGM), and 21 of polycythemia vera (P. vera), and 30 from healthy control persons were evaluated morphometrically in sections of undecalcified plastic-embedded core biopsies. Clear distinctions were revealed in size of megakaryocytes, nuclear lobulation, clustering, and the nuclear size and shape of megakaryocytes. Nuclear size and cellular size were significantly less in CML (range of means of cellular size: 220-360 microns2) than in the other three Ph1-negative groups (range of means: 480-750 microns2). Nuclear lobulation was more distinct in PTH than in P. vera, and especially in CMGM. Clustering of megakaryocytes was more than twice as frequent in CMGM (8.0-10.5%) as in any of the other three groups (0.1-7.0%). Naked nuclei were more numerous in all groups of CMPD. The main topic of the study is the different size of megakaryocytes in the four main groups of CMPE, allowing a distinction between small-megakaryocytic Ph1-positive CML and large-megakaryocytic Ph1-negative forms of CMPD.
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PMID:[Morphometry of megakaryocytes for supporting the histologic diagnosis of chronic myeloproliferative diseases]. 788 12

The histopathological classification of chronic myeloproliferative disorders can be supported by applying cytogenetics and molecular genetics to the analysis of bone marrow or blood cells, as demonstrated in 253 cases evaluated. The Philadelphia translocation (9;22) is the most important genetic parameter, being specific for chronic myeloid leukemia. Conventional methods for the detection of the t(9;22) are karyotyping and Southern blot analysis of the bcr gene. The newly established technique of fluorescence in situ hybridization (FISH) allows visualization of bcr-abl fusion even in non dividing cells. Molecular cytogenetics for t(9;22) yield results that are rapid and reliable as well as easily quantifiable.
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PMID:[Cytogenetics and molecular studies confirm the histopathologic diagnosis of chronic myeloproliferative diseases]. 788 13

A morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen--PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa) to evaluate endoreduplicative activity of megakaryopoiesis. In addition to a control group, patients included different subtypes of chronic myeloproliferative disorders (CMPDs) like chronic myeloid leukaemia (CML), polycythaemia vera (P. vera), primary thrombocythaemia (PTH) and finally primary (idiopathic) osteomyelofibrosis (OMF). In comparison with the normal bone marrow and also with P. vera and PTH a significant increase in PCNA-labelling (late G1 and S phases) of megakaryocytes was recognizable in OMF, contrasting with a striking reduction of this marker in CML. Particularly in advanced stages of OMF, secondary folate deficiency leading to a megaloblastoid appearance of erythroid precursors is a frequent finding. In pernicious anaemia previous cytokinetic studies have demonstrated an arrest in the S phase (DNA synthesis) of the cell cycle due to vitamin B12/folate (haematinic) deficiency. A similar pathomechanism may also be effective in OMF. Consequently, a block in the S phase of the cell cycle is assumed which is in keeping with the increased numbers of PC10-positive megakaryocytes. Significant correlations were calculable between megakaryocyte sizes and PCNA-staining capacity in the normal bone marrow and CMPDs. According to morphometry small-sized (hypoploid) megakaryocytes showed a prevalence of PCNA labelling. This finding is confirmative with a hypothesis on the dynamics of endoreduplicative activity of megakaryocytes, i.e. the prolongation of G1/G2 phases in larger (polyploid) elements. On the other hand, some of the giant polyploid megakaryocytes may cease endoreduplication and enter into G0 phase, which could partially explain the predominance of PCNA-negative large-sized cells of this lineage.
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PMID:Megakaryopoiesis in chronic myeloproliferative disorders: immunohistochemical evaluation of endoreduplicative activity by PCNA-staining reaction. 798 Nov 37

Essential thrombocythemia (ET), one of the chronic myeloproliferative disorders, is a clonal disorder of multipotent stem cells. Although most patients with ET have a prolonged benign course, a minority of patients may develop a blastic crisis similar to chronic myelogenous leukemia (CML). A case of ET terminating in blastic crisis 8 years after the initial diagnosis is presented. The blast cells were cytochemically and immunophenotypically consistent with the acute myelogenous leukemia with minimal myeloid differentiation subtype of the FAB classification. From the review of the literature on blastic transformation of ET, acute leukemia with an M4 or M7 phenotype occurred more frequently. In addition, three valuable factors to predict the leukemic transformation of ET appear to be karyotypic abnormalities, such as involvement of chromosome 21, previous therapies with a mutagenic potential, and the capability of bone marrow cells to form in vitro spontaneous colonies as in CML.
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PMID:Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation--a brief review of recent literature. 802 50

The reliability of histopathological diagnosis in bone marrow specimens from patients with chronic myeloproliferative disorders (CMPD) was evaluated by correlating the histological findings with molecular genetic and cytogenetic analyses of the Ph1-translocation. A rearrangement of m-bcr was detected only in patients (28/30) diagnosed histologically as chronic myeloid leukemia (CML). This finding was supported by the presence of a Ph1-chromosome in 24/26 patients with CML examined. All the patients with other types of CMPD, including polycythemia vera (PV), primary thrombocythemia (PTH) and chronic megakaryocytic-granulocytic myelosis (CMGM), as well as those with unclassifiable CMPD (CMPD.UC) were Ph1-negative (n = 38). The histopathological discrimination of CML from Ph1-negative varieties of CMPD was also reliable for patients with myelofibrosis complicating CML, CMGM and CMPD.UC. The results demonstrate that bone marrow histopathology allows a reliable diagnosis of CML. This is in contrast with hematological data such as high platelet counts which show considerable overlapping in the various forms of CMPD.
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PMID:Evidence from molecular genetic and cytogenetic analyses that bone marrow histopathology is reliable in the diagnosis of chronic myeloproliferative disorders. 809 57

We have investigated the involvement of tumor suppressor genes (p53 and RB1) and dominantly acting oncogenes (Ras family genes) in BCR/ABL positive and negative chronic myeloproliferative disorders (CMPD) at different stages of the disease, including 26 cases of BCR/ABL+ chronic myeloid leukemia (CML) blast crisis, 9 myelosclerosis with myeloid metaplasia, 4 polycythemia vera, 10 essential thrombocythemia, 1 juvenile CML, and 8 BCR/ABL- CML. The presence of mutations in p53 exons 5 through 9, as well as in RB1 exons 10-27 and in N-, K-, H-Ras exons 1 and 2 was tested by the PCR-Single Strand Conformation Polymorphism technique and by PCR-Direct Sequencing. In addition, Southern blot analysis was used to investigate the occurrence of gross rearrangements in the p53 gene as well as loss of heterozygosity at 17p13, the site of p53. Acute phase BCR/ABL-CMPD cases displayed a high frequency of p53 (2/7) and Ras (3/7) lesions, whereas BCR/ABL- CMPD in chronic phase displayed only germline p53 and Ras sequences. Conversely, p53 inactivation was restricted to only 1/26 cases of BCR/ABL+ CML blast crisis. No alterations in the RB1 gene were detected in any of the cases analyzed. These data indicate that p53 inactivation and/or Ras activation might play a role in acute transformation of BCR/ABL- CMPD and that the molecular mechanisms of tumor progression may be different in BCR/ABL+ versus BCR/ABL-CMPD.
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PMID:Molecular mechanisms of tumor progression in chronic myeloproliferative disorders. 815

Bcr-abl mRNA expression was studied in patients with chronic myeloproliferative disorders (CMPD) by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. A bcr-abl transcript was not found in any patient with polycythemia vera, essential thrombocythemia or primary myelofibrosis, suggesting that the bcr-abl rearranged clone is not present in CMPD other than chronic myelogenous leukemia (CML). In CML clinical and laboratory data were compared from three bcr-abl types: the bcr exon 2-abl exon 2 (B2-A2) type, bcr exon 3-abl exon 2 (B3-A2) type and the co-expression type. Age at diagnosis tended to be younger (p = 0.08) in the co-expression type, and the platelet count tended to be lower (p = 0.11) in the B2-A2 type. However, there was no difference in other data, including the duration of the chronic phase and the phenotype of blasts at blast crisis.
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PMID:Bcr-abl mRNA expression in patients with chronic myeloproliferative disorders--absence of bcr-abl fused clone except chronic myelocytic leukemia. 825


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