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)

We describe a case of Philadelphia-negative essential thrombocythemia in whom bcr-abl hybrid messenger RNA was detected. The patient suffered from frequent splenic infarctions and myelofibrosis. Interestingly, a transformation to acute leukemia which was commonly seen in patients with bcr-abl-positive chronic myelogenous leukemia did not occur until he died from heart failure due to severe anemia 8 years after the diagnosis. The heterogeneity of bcr-abl-positive thrombocythemia is emphasized.
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PMID:bcr-abl hybrid messenger RNA in a patient with Philadelphia-negative essential thrombocythemia. 754 25

Chronic myeloproliferative diseases, such as chronic myeloid leukemia and polycythemia vera, are associated with neutrophil dysfunction. Very little data is available on essential thrombocythemia (ET). In the current study we evaluated 21 patients with ET. All patients were studied at least 16 weeks after any cytostatic therapy and 10 days after any other therapy. Neutrophil functions were investigated as follows: flow cytometric evaluation of whole blood phagocytosis of opsonized FITC-conjugated E. coli; whole blood chemiluminescence after stimulation with opsonized zymosan and evaluation by an automated, computer-assisted luminometer (LB 950, Berthold); and chemiluminescence and superoxide anion generation by purified neutrophils after f-MLP and PMA stimulation. Chemiluminescence and superoxide anion generation after f-MLP stimulation were found to be significantly lower than in normal subjects, whereas values within the normal ranges were registered after PMA stimulation. Phagocytosis-associated chemiluminescence was found to be impaired both by using zymosan opsonized with autologous plasma and zymosan opsonized with normal plasma, despite a normal phagocytic activity. These data show the presence in ET of a complex neutrophil dysfunction that may be related to an impaired signal transduction during both the phagocytic process and f-MLP stimulation.
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PMID:Neutrophil functions in essential thrombocythemia. 762 97

Plasma and platelet von Willebrand factor (vWF) measurements, multimeric pattern and subunit composition of plasma vWF were obtained in 29 consecutive patients with chronic myeloproliferative syndromes. In the 8 patients with chronic myelogenous leukemia (CML), plasma vWF was significantly higher than in the 11 patients with essential thrombocythemia (ET) and in the 10 patients with polycythemia vera (PV). The RiCof/vWF:Ag ratio was low in all these groups of patients (mean 0.64 +/- 0.1, 0.66 +/- 0.2, and 0.61 +/- 0.2; normal 0.97 +/- 0.2). Bleeding time was prolonged (> 7.5 min) in 1/8 CML patients, 1/10 with PV, and 3/11 with ET. Plasma vWF multimers showed a minor loss of the largest multimers in 3/8 patients with CML, 4/10 with PV, and a more severe reduction in 9/11 ET patients. The latter pattern correlated with an abnormal proteolysis of vWF, expressed by a major increase of the 140-Kd fragment and decrease of the intact 225-Kd subunit in ET patients, whereas the 176-Kd fragment was significantly increased in all the subgroups of patients. Platelet vWF was significantly higher in CML patients in comparison to ET and normal controls. However, minor losses of the larger multimers were evident in all the subsets of patients. In ET patients also the intermediate forms were lacking in platelets, accompanied by a significant decrease of platelet RiCof. This abnormality was significantly correlated with the occurrence of bleeding symptoms in PV and ET patients (P = 0.007; Fisher's exact test). In conclusion, plasma and platelet vWF abnormalities are common findings in myeloproliferative syndromes and are more severe in ET. The more pronounced platelet vWF abnormalities in ET may reflect the more frequent bleeding symptoms observed in this disorder.
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PMID:Platelet von Willebrand factor abnormalities in myeloproliferative syndromes. 763 73

The incorporation of other marrow cells into megakaryocytes, termed emperipolesis, has been studied in paraffin biopsy sections from 17 untreated patients with myeloproliferative disorders (MPDs). The group consisted of 12 females and 5 males, aged from 34 to 72 years (mean 51.3). Patients with essential thrombocythemia (ET)--9, chronic granulocytic leukemia (CGL)--4, polycythemia vera (PV)--3, and myelofibrosis (MF)--1 were included into the study. Clusters of large polyploid megakaryocytes were observed in anatomic relation to the marrow sinusoidal system. Emperipolesis has been scored as being present or absent per 100 megakaryocytes/slide. Cells found within megakaryocytes were mostly erythroblasts and mature granulocytes. The number of incorporated cells varied from 1 to 7 per one megakaryocyte. Considering the 17 patients with MPDs, emperipolesis was observed in a vast majority of those with ET(8/9) and PV(2/3), in some with CGL(1/4), but not in MF. The mechanism of megakaryocytic emperipolesis remains unclear. Adhesion molecules on megakaryocytes and incorporated cells may possible mediate the cell-to-cell interactions important for emperipolesis.
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PMID:[Emperipolesis in megakaryocytes in patients with thrombocytosis in the course of myeloproliferative disorders]. 765 23

Microsatellite instability is a newly identified mechanism of mutation that occurs in some heritable neurological and muscular disorders, as well as in an increasing number of human cancers. To extend previous data, we examined the genetic instability of a human genomic region, termed S3/1, which we isolated from a human DNA library. The S3/1 sequence contains a stretch with exceptionally high numbers of (GA)n and (CA)n dinucleotide repeats. An interesting rearranged pattern emerged from Southern blot analysis of genomic DNA from three patients with different hematopoietic proliferative diseases out of 69 analyzed (one case of essential thrombocytosis (ET), one of chronic myelogenous leukemia (CML) and one of acute myelogenous leukemia (AML)). The CML and ET patients showed a deletion of 300 to 400 base pairs (bp), and the AML an insertion of about 600 bp, involving the S3/1 locus. Amplification of the rearranged fragments confirmed these observations, and enabled a precise analysis of the region involved. In normal individuals, no gross rearrangements involving this region could be detected. Analysis of DNA from three consecutive bone marrow biopsies of the CML patient disclosed that the genetic alteration affecting S3/1 was no longer detectable following alpha 2-interferon therapy, neither by Southern blot nor by polymerase chain reaction (PCR), thus confirming the tumor-specificity of the alteration; in the same patient, moreover, two out of five other analyzed microsatellites showed tumor-specific alleles, suggesting a more generalized genetic instability in the leukemic cells. These results demonstrate genetic instability of a region containing high numbers of short dinucleotide repeats in a small percentage (4%) of human hematopoietic proliferative disorders.
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PMID:Genetic instability of a dinucleotide repeat-rich region in three hematologic malignancies. 765 21

In hematological diseases such as myeloproliferative disorders (MPD) or myelodysplastic syndromes (MDS), some abnormalities in the chemiluminescence of neutrophils are observed. There are two groups; one includes chronic myelogenous leukemia (CML), essential thrombocythemia (ET) and MDS, which all have decreased chemiluminescence of neutrophils. The other group includes polycythemia vera (PV) which has increased neutrophil chemiluminescence. We studied the neutrophil function by analyzing the chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in 35 patients with hematological diseases. In most of these cases the defects in chemiluminescence in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were correlated with those in response to phorbol 12-myristate 13-acetate (PMA). But there were exceptional cases in which the maximal light emission of chemiluminescence (Max CL) in response to FMLP was obviously lower than controls despite the fact that the Max CL in response to PMA was the same as the controls. These facts suggest a heterogenicity of the defect site in these diseases. There was a correlation between the level of chemiluminescence and the neutrophil alkaline phosphatase (NAP) activity in these patients. In vitro culture of CML neutrophils with granulocyte colony-stimulating factor (G-CSF) showed a correlation between the increase in the level of chemiluminescence and NAP activity. These results suggest that NAP may take part in the control of neutrophil function.
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PMID:Chemiluminescence of neutrophils in patients with myeloproliferative or myelodysplastic hematologic diseases--relation to neutrophil alkaline phosphatase activity. 768 68

We described a fully automated measurement of reticulated platelets using a fluorescent dye, auramine O, and a reticulocyte counter, the R-3000, equipped with special software. Reproducibility and linearity were shown to be good. In the normal subjects studied (n = 60), the mean value for reticulated platelets was 0.98% +/- 0.41% and the mean absolute count was 2.12 +/- 0.69 x 10(9)/l. The absolute count for reticulated platelets was significantly lower (p < 0.05) in patients with reduced thrombopoiesis as seen in acute myeloblastic leukemia, aplastic anemia or chemotherapy-induced thrombocytopenia and it was elevated (p < 0.05) in essential thrombocythemia and in chronic myelocytic leukemia with thrombocytosis. All 20 patients with chronic idiopathic thrombocytopenic purpura had a high percentage of reticulated platelets. The percentage of reticulated platelets was significantly increased (p < 0.05) in patients with impaired thrombopoiesis despite the reduction in the absolute count. In 2 leukemic patients, an apparent rise was noticed in the percentage of reticulated platelets which preceded by several days a progressive increase in the platelet count at the recovery phase of thrombocytopenia. The results suggest that an automated measurement of reticulated platelets can be applied to routine laboratories for clinical use.
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PMID:Automated measurement of reticulated platelets in estimating thrombopoiesis. 772 Aug 36

Development of the method to determine reticulated platelets is briefly reviewed. A new rapid method to automatically count reticulated platelets is very recently established by our research group. The principle of the measurement of reticulated platelets is based on flow cytometry. The platelets are quickly stained with a RNA fluorescent dye, auramine O and fluorescent intensity (RNA content) and forward scatter (cell size) are measured in only 80 seconds with a reticulocyte counter, equipped with special software for analysis of reticulated platelets. Both of the reproducibility and the linearity were shown to be good. Normal percentage value for reticulated platelets was 0.98% +/- 0.41% and its absolute count was 2.12 +/- 0.69 x 10(9)/l. The absolute count was decreased in patients with reduced thrombopoiesis such as acute myeloblastic leukemia, aplastic anemia and was elevated in patients with essential thrombocythemia and in chronic myelocytic leukemia. The patients with chronic idiopathic thrombocytopenic purpura had a high percentage of reticulated platelets. An apparent rise was noticed in the percentage of reticulated platelets which preceded by several days a progressive increase in the platelet count at the recovery phase of thrombocytopenia in a couple of leukemic patients. These suggest that an automated measurement of reticulated platelets can be clinically useful to estimate thrombopoiesis in bone marrow.
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PMID:[Reticulated platelets--automated measurement and clinical utility]. 778 28

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 Ph1-negative groups of chronic myeloproliferative diseases (CMPD) are described, and histopathological criteria that distinguish them from each other are given. These are based upon observations in primary biopsies from 2,331 patients with CMPDs among a total of 34,160 patients referred between 1 January 1989 and 30 June 1994 to the Bone Marrow Registry. These cases of CMPD break down into the main groups as follows: CML 23.2%, megakaryocytic myelosis consistent with agnogenic myeloid metaplasia 22.3%, essential thrombocythemia 22.1%, and polycythemia vera 20.4%; 12.0% of cases were unclassifiable. Histological progress in each group is characterized by (1) increasing number and pleomorphy of megakaryocytes, (2) increasing fibrosis, and (3) excess of blasts. These three features can be observed in diagnostic biopsies before any therapy. Therefore, it is recommended that such alterations be reported semiquantitatively. A staging system with four stages from 0 to 3 for each of the three features is introduced. Its application allows staging for the individual patient on the basis of diagnostic biopsies.
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PMID:[Histopathology of Ph1-negative chronic myeloproliferative diseases]. 788 16


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