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 aim of the present study was to evaluate the significance of immunomorphometric assessment of megakaryocyte size and number in normal and pathologic human bone marrow. Thus, we compared morphometric characteristics of megakaryocytes in 56 bone marrow trephine biopsies stained by immunohistochemical and conventional techniques. Morphometric results showed that precise megakaryocyte size in normal and pathologic samples can be calculated even by using conventional staining technique, but only employing specific stereological corrections. Immunomorphometric evaluation revealed populations of "small" megakaryocytes (< 14 microns), "morphologically unrecognized" by conventional staining technique (promegakaryoblasts in normal and stimulated as well as micromegakaryocytes in pathologic bone marrow). In patients with normal and stimulated megakaryocytopoises percentage of "small" megakaryocytes was generally low (10.6% and 14%, respect.); so, megakaryocyte number was similar in immunohistochemically and conventionally stained sections. In contrast, percentages of "small" megakaryocytes were significantly higher in patients with stem cell disorders (namely, myelodisplastic syndrome and chronic granulocytic leukaemia), as compared to controls (35.3% in MDS; 22.9% in CML and 10.6% in controls). In those patients megakaryocyte numbers were more sensitively detected by immunohistochemistry than by conventional staining.
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PMID:[Importance of immunomorphometric evaluation of the size and number of megakaryocytes in normal and pathologic bone marrow]. 771 37

Spontaneous colony formation from bone marrow megakaryocyte progenitors (BMsCFU-Mk) was studied in 24 patients with essential thrombocythaemia (ET), 20 patients with reactive thrombocytosis (RT), 20 patients with polycthaemia rubra vera with thrombocytosis (PRVtr), 16 patients with chronic myeloid leukaemia with thrombocytosis (CMLtr) and 18 normal control subjects (C). The culture medium which was used in the methylcellulose assay in vitro contained 30% of plasma from a single patient with hereditary haemochromatosis. Remarkable BMsCFU-Mk growth was recorded in all patients with ET but in none with RT or in C. BMs-CFU-Mk were present in 11/20 patients with PRVtr and 7/16 patients with CMLtr. Spontaneous bone marrow erythroid progenitors (BMsBFU-E) were also determined in these patients. BMsBFU-E were found in 21/24 patients with ET and none in the patients with RT and C. All patients with PRVtr and one patient with CMLtr showed BMsBFU-E. We conclude that our implementation of the in vitro methylcellulose assay allows the BMsCFU-Mk to be used as an unequivocal test for discrimination between ET and RT which has not been shown in previously published studies. In addition, we present evidence that in 10 patients BMsCFU-Mk and/or BMsBFU-E growth in the test persisted after long-lasting haematological remission.
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PMID:The determination of spontaneous megakaryocyte colony formation is an unequivocal test for discrimination between essential thrombocythaemia and reactive thrombocytosis. 779 51

Two leukemia cell lines, TS9;22 and YS9;22, were established from different individuals with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in blast crisis. The reverse transcript-polymerase chain reaction (RT-PCR) technique revealed that both cell lines expressed GATA-1, GATA-2, and the stem cell leukemia (SCL) gene, consistent with a megakaryocyte lineage. Chromosome analysis revealed that TS9;22 cells show the Ph translocation without abnormality of chromosome 3. In contrast, YS9;22 cells show the Ph translocation and dic(3)(q26;p12). Northern analysis revealed that YS9;22 cells express the EVI1 (ecotropic virus integration-1) gene, possibly because of the chromosomal translocation in the 3q26 region; TS9;22 cells do not express EVI1. However, no rearrangements were detected over 600 kb upstream or over 900 kb downstream of EVI1 in the YS9;22 cell line, suggesting a different mechanism of EVI1 activation from that in leukemia cells with either a t(3;3)(q21;q26) or inv(3)(q21q26). These results indicate that EVI1 expression in YS9;22 cells is linked to the 3q26 abnormality and that EVI1 activation plays an oncogenic role in the blastic transformation of chronic myeloid leukemia.
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PMID:EVI1 expression associated with a 3q26 anomaly in a leukemia cell line derived from the blast crisis of chronic myeloid leukemia. 780 6

We have established a novel human megakaryoblastic cell line, designated as MEG-A2, from a patient with megakaryoblastic crisis of Philadelphia (Ph) chromosome positive chronic myelogenous leukemia. MEG-A2 cells showed positive phenotypes for periodic acid Schiff and alpha-naphthylbutyrate esterase reactions, but were negative for myeloperoxidase and naphthol ASD chloroacetate esterase reactions. Flow cytometric analyses of cell surface markers revealed that MEG-A2 cells had a low level of GP IIb/IIIa expression as well as apparent expressions of CD4, CD7, CD13, CD33 and CD34 antigens, but no expression of GP Ib nor glycophorin A. Stimulation with phorbol 12-myristate 13-acetate (PMA) dramatically increased the expression of megakaryocyte-related markers such as HPL-3, J15, Pit-1, Y2/51 and AN51 in MEG-A2 cells. The PMA-stimulation also induced expression of platelet peroxidase (PPO) in MEG-A2 cells on electromicroscopic observation. Proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or erythropoietin were observed, and the expression of GP IIb/IIIa was increased by stimulation with GM-CSF, IL-3, erythropoietin and interleukin-6 (IL-6). Protein S mRNA expression was seen in cultured cells on Northern blot analysis. Expression of platelet factor 4 mRNA was induced in PMA-stimulated cells, and a marked accumulation of protein was observed in the culture medium. In conclusion, a new cell line, MEG-A2, belongs to the relatively immature megakaryocytic lineage and has markedly increased megakaryocytic characteristics with PMA stimulation.
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PMID:Establishment and characterization of an immature human megakaryoblastic cell line, MEG-A2. 786 73

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens in 60 patients with chronic myeloid leukemia (CML) to quantify erythropoiesis and its proliferation capacity and to assess the stainable marrow iron (hemosiderin). For this purpose, an elaborate double-immunostaining technique was applied. This included a monoclonal antibody (PC10) that is directed against proliferating cell nuclear antigen (PCNA), followed by an antibody against glycophorin C (Ret40f), to identify all nucleated erythroid precursor cells. Additionally, morphometric data were derived from immunostaining of megakaryocytes (CD61) and macrophages (PG-M1), including its hemosiderin-laden subpopulation. Finally the determination of argyrophilic (reticulin) fiber density was carried out. In comparison with a control group (15 patients) without any hematologic disorder, in CML patients morphometric evaluation showed a significant reduction in the number of erythroblasts and normoblasts. This feature was associated with a PCNA-labeling index within the normal range and a decreased stainable marrow iron (number of hemosiderin-storaging macrophages). Several parameters were established to exert a predictive value on survival. A worsening of prognosis was associated with a decrease in the number of erythroid precursors (< 460/mm2), a low hemoglobin level (< 10 g/dl), a high megakaryocyte count (> 50 cells/mm2), an increased density of reticulin fibers (> 30 i x 10(2)/mm2) and splenomegaly (> 15 cm below costal margin). Our findings are in keeping with results obtained from in vitro studies of cell proliferation in CML, which is not significantly altered in comparison with the normal bone marrow. Finally, the present data, although derived from a small group of patients, emphasize the impact of histologic variables to be included in one of the major clinical trials on prognosis in CML.
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PMID:Erythropoiesis in CML--immunomorphometric quantification, PCNA-reactivity, and influence on survival. 790 86

This report describes a patient presenting with acute myeloid leukaemia (AML-FAB classification M2). Phenotypic markers were positive for cells of the myeloid lineage, but negative for monocyte/macrophage, megakaryocyte, and T-cell lineages. The occasional blast was positive for CALLA. All blasts carried the Philadelphia chromosome (Ph+), with 20% also harbouring a monosomy 7 (a cytogenetic marker for AML). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the presence of two BCR/Abl mRNA transcripts; b2a2, the CML-type and E1a2, the ALL-type. Immunoglobulin (Ig) gene analysis demonstrated the presence of a small population of cells containing rearranged Ig genes. After a short remission, the patient relapsed. At relapse the leukaemia had undergone a major phenotypic switch from AML to ALL, with blasts bearing B-cell markers. Ig gene analysis confirmed a monoclonal population of B-cells. The Ph+ persisted, but the monosomy 7 had disappeared. The same two BCR/Abl mRNA transcripts were found at relapse as at presentation. To our knowledge, this is the first report of an AML simultaneously expressing BCR/Abl transcripts from both the minor and major BCR. The possible mechanisms of this dual expression are discussed.
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PMID:A Ph+ acute myeloid leukaemia expressing both CML-type and ALL-type BCR/ABL mRNA transcripts. 795 Sep 25

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

To evaluate the prognostic significance of clinical as well as histological disease features at the time of diagnosis, an immunohistochemical and morphometric study was performed on bone marrow trephine biopsies in 130 patients with Ph(1+)-CML. For identification of all cell elements of the megakaryocytopoiesis we used the monoclonal antibody CD61 (Y2/51) and for the macrophages, the recently characterized antibody PG-M1. Density of argyrophilic fibers was determined per fat cell-free marrow area. Based on a multivariate analysis-derived risk model, the reproducibility of the prognostic score described by Sokal and co-workers was tested, particularly with regard to histological variables. Additionally, we calculated the disease-specific loss in life expectancy. Our prognostic model (Cox model) consisted of the variables: age, spleen size, peripheral erythro-normoblasts, pseudo-Gaucher cells, and fiber density. To assess the validity of this new CML score, a receiver-operating curve (ROC) of sensitivity and specificity was constructed. The improved prognostic efficiency of this newly developed risk model in predicting death within 3 years after diagnosis of CML was demonstrated in comparison with generally accepted staging systems. Immunohistochemistry revealed that not the total number of macrophages, but only the subfraction of pseudo-Gaucher cells exerted a significant impact on survival. Furthermore, it was feasible to calculate the number of atypical micromegakaryocytes and pro- and megakaryoblasts. This abnormal and immature cell population showed a significant correlation with fiber density and prognosis. Finally, the practical value of the Hannover classification was tested. This histological classification enabled a discrimination between two groups with different survival patterns, i.e., granulocyte and/or megakaryocyte-rich subtypes versus subtypes with increase in reticulin and collagen fibers.
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PMID:Histological features of prognostic significance in CML--an immunohistochemical and morphometric study (multivariate regression analysis) on trephine biopsies of the bone marrow. 831 59

Formation of the Philadelphia (Ph1) chromosome, which contains the hybrid bcr-abl gene, is thought to be the initial event in chronic myelogenous leukemia (CML). The positions of the breakpoint within the breakpoint cluster region (bcr) on the bcr-abl gene in 22 chronic-phase cases of Ph1-positive CML were determined using conventional Southern blots, and the splicing pattern were also determined the species of the fused bcr-abl mRNA in 79 CML cases using the polymerase chain-reaction procedure (RT-PCR). The location of the breakpoint within the bcr locus was assigned to one of five zones. Breakpoints in zones 1 and 2 were grouped as 5', and those in zones 3, 4 and 5 as 3'. Nine patients had 5' breakpoints and 13 patients had 3' breakpoints. The platelet counts of 3' patients were significantly higher than those of 5' patients (1395 vs 274 x 10(9)/L; p < 0.03). The megakaryocyte counts from bone marrow histological sections in 3' patients (n = 12) and 5' patients (n = 7) were 63.4/mm2 and 19.5/mm2, with a significant difference at p < 0.006. The mean number of megakaryocyte progenitor cells assayed by in vitro cloning was 128.3/2 x 10(5) bone marrow cells for 3' patients (n = 7) compared with 46.3 for 5' patients (n = 4). Using the RT-PCR technique, the bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 18 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 45 patients, and both types of mRNA were detected in 16 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relationship between the type of bcr-abl hybrid messenger RNA and thrombopoiesis in Philadelphia-positive chronic myelogenous leukemia. 837 29

Interleukin-4 (IL-4) is a cytokine with pleiotropic activities. In normal bone marrow cultures grown in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), IL-4 suppresses granulocyte-macrophage colony-forming unit (CFU-GM) proliferation but it enhances the colony-stimulatory effect of granulocyte colony-stimulating factor (G-CSF). We studied the effect of IL-4 on chronic myelogenous leukemia (CML) bone marrow or peripheral blood cells from 30 patients using the CFU-granulocyte-erythrocyte-monocyte-megakaryocyte colony culture assay. In several repetitive experiments, IL-4 inhibited CFU-GM colony replication by 24 to 65% in a dose-dependent fashion at concentrations ranging from 0.01 to 10 micrograms/ml when patients' cells were cultured in the presence of erythropoietin alone or with phytohemagglutinin-conditioned medium, GM-CSF, or IL-3. The addition of 100 U/ml of IL-1 beta to the CML cultures partially reversed the inhibitory effect of IL-4. Incubation of CML low-density peripheral blood cells with IL-4 resulted in down-regulation of IL-1 beta and IL-6 production in three of four samples, suggesting that the suppressive effect of IL-4 is mediated by inhibition of IL-1 and by other mechanisms including inhibition of IL-6 production. In contrast to the stimulatory effect exerted by IL-4 on G-CSF-dependent CFU-GM progenitor proliferation in normal marrow, the addition of IL-4 to CML cultures grown in the presence of G-CSF resulted in a divergent effect: suppression of CML CFU-GM in two, stimulation in three, and no significant effect in two CML patients' samples. It is therefore possible that IL-4 may have an in vivo antiproliferative effect in a subpopulation of CML patients.
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PMID:Suppression of chronic myelogenous leukemia colony growth by interleukin-4. 842 75


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