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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 correlations between select clinical and laboratory data recorded at the time of diagnosis in 125 chronic myelogenous leukemia patients (60 men and 65 women) and survival time these patient was analysed. All patients were treated with similar methods. Characteristics for which there was evidence of associations with shorter survival outcome were older age, anemia, high percentage of peripheral and marrow blasts and thrombocytopenia or thrombocytosis. There was no evidence of statistically significant prognostic value such parameters as: sex, presence of symptoms, hepatosplenomegaly, high leukocytosis (WBC), high proportion of circulating promyelocytes, neutrophils and eosinophils and serum LDH or leukocyte alkaline phosphatase activity. Peripheral basophilia appeared to have advantage prognostic relevance to survival time. The median survival time observed patients was 38-65 months.
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PMID:[Prognostic significance of some clinical and laboratory parameters in patients with chronic myelogenous leukemia]. 778 14

We report a highly sensitive time-resolved immunofluorometric method for quantification of polymerase chain reaction (PCR)-amplified mRNA sequences. The PCR primers are labeled at their 5' ends, one with biotin and the other with a hapten. The modified primers are incorporated, during PCR, in the amplified product. The PCR product is captured, through its biotin moiety, to a streptavidin-coated solid phase and subsequently is detected with an alkaline phosphatase-labeled antibody. The phosphate ester of fluorosalicylic acid is used as a substrate. The fluorosalicylate produced forms a highly fluorescent ternary complex with Tb(3+)-EDTA, which is measured by time-resolved fluorometry. We chose the determination of PCR-amplified chronic myelogenous leukemia-specific mRNA as a model system. mRNA molecules corresponding to 0.1 leukemic cell in the presence of 0.5 million normal cells may be detected (signal-to-background ratio of 1.5). The method provides a sensitive and rapid nonisotopic alternative to Southern blot and hybridization with radioactive probes.
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PMID:Time-resolved immunofluorometric determination of specific mRNA sequences amplified by the polymerase chain reaction. 784 30

We report here two cases of a previously undescribed myeloproliferative disorder. Both were young adult males who presented with generalized lymphadenopathy, splenomegaly, leukocytosis, polycythemia, and persistent thrombocytopenia. The leukocyte alkaline phosphatase (LAP) score was low in both cases, and the bone marrow was hypercellular without dysplasia or fibrosis, but lacked the Philadelphia chromosome, BCR gene rearrangement, or other karyotypic abnormalities. The clinical course was indolent in each case. One patient died from an unusual "blast crisis" after 12 years, while the second patient remains in a complete hematologic remission on hydroxyurea and alpha interferon 4 years from diagnosis. Interestingly, changes in therapy in this patient have consistently resulted in precise and concerted fluctuations in his blood counts, with the red and white cells cycling together and the platelets and mean corpuscular volume (MCV) changing concomitantly but in the opposite direction. This unique myeloproliferative disorder is distinguishable from all previously described forms of chronic myeloid leukemia and other myeloproliferative syndromes.
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PMID:A new myeloproliferative syndrome. 786 27

Decreased neutrophil alkaline phosphatase (NAP) synthesis is a classical feature of Philadelphia (Ph) positive chronic phase chronic myeloid leukemia (CML). Whether this aberration is an integral leukemic property of the cell or results from mediation by other factors is unclear. During alpha-interferon (alpha-IFN) based therapy the relationship between Ph chromosome suppression and NAP synthesis was examined. Four categories of response were observed in 19 patients studied sequentially. Significantly, persistent low NAP activity was observed in one patient in complete cytogenetic remission, while a second group of 7 patients demonstrated normal NAP activity in spite of persistence of the Ph chromosome in 100% of metaphases. In the absence of various clinical influences that can modulate NAP activity in chronic phase CML, the results reinforce the observation that the BCR/ABL fusion gene product is not a key factor influencing NAP activity in CML.
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PMID:Discordant neutrophil alkaline phosphatase activity and cytogenetic response in chronic myeloid leukemia treated with alpha-interferon. 816

Two-thirds of patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukaemia (ALL) have a breakpoint in the minor breakpoint cluster region (m-bcr) of the BCR gene, which results in an e1a2 transcript and a P190BCR-ABL fusion protein. This type of genomic rearrangement occurs very rarely in chronic myeloid leukaemia (CML); it has been reported in only four cases. We describe here a fifth case of P190 CML in which the cytomorphological characteristics were intermediate between CML and chronic myelomonocytic leukaemia (CMML). This case, and the four reported previously, had a consistent and significant monocytosis with a low neutrophil/monocyte ratio in the peripheral blood, resembling CMML. On the other hand, they also had a high percentage of circulating immature granulocytes, basophilia and low neutrophil alkaline phosphatase (NAP) score, which are more commonly found in classical CML. Thus, P190 CML may be a specific form of CML, in which the myeloproliferative process includes the monocytic, as well as the granulocytic lineage. Since the molecular defect in CML is thought to involve a pluripotent stem cell, the different effects of P210BCR-ABL and P190BCR-ABL in CML must reflect the somewhat wider spectrum of activity of the P190BCR-ABL. Other patients with atypical CML or CMML who lack a Ph chromosome may also have an m-bcr breakpoint which would not be detected on standard Southern blots, but which would be detectable by polymerase chain reaction amplification of reverse transcribed RNA.
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PMID:P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia? 793 80

A previously healthy 11 year-old-white boy presented with persistent mild leukocytosis and a posterior mediastinal mass. Surgical excision of the mass showed it to be a ganglioneuroma. Postoperatively, the patient had marked leukocytosis (white blood cell count 57,000/mm3) and a low leukocyte alkaline phosphatase score. Bone marrow aspirate for cytogenetics performed in the evaluation of the posterior mediastinal mass showed the presence of the Philadelphia chromosome (Ph) in 19 of 20 metaphase spreads. The diagnosis of Ph+ chronic myeloid leukemia (CML) was confirmed on repeat cytogenetics. Subsequent detailed skin examination showed six small cafe-au-lait spots but no other evidence of neurofibromatosis. This is the first report to describe an association between ganglioneuroma and Ph+ CML.
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PMID:Philadelphia chromosome-positive chronic myeloid leukemia and thoracic ganglioneuroma. Previously undescribed association. 844 51

A 79-year-old man who had been diagnosed as having sarcoidosis when he was 63 year old, was admitted to our hospital because of marked thrombocytosis and leukocytosis in July 1991. The low neutrophil alkaline phosphatase (NAP) score, presence of Philadelphia (Ph1) chromosome in the bone marrow cells, and M-BCR rearrangement by Southern blot hybridization were observed. He was diagnosed as having chronic myelogenous leukemia complicated with sarcoidosis. The coexistence of sarcoidosis and leukemia has rarely been reported. It is difficult to discuss that there is not causal association between of them.
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PMID:[Chronic myelogenous leukemia complicated with sarcoidosis]. 845 Jun 15

Neutrophil granulocytes are the most important white blood cells in the combat of non-viral infections. Circumstantial evidence indicates that neutrophils in addition modulate the inflammatory process. Production of neutrophils takes place in the bone marrow, and mature cells egress to the circulation. Neutrophils emigrate following activation from the vessels into the tissues (chemotaxis). During this process neutrophils generate reactive oxygen species (respiratory burst) and mobilize intracellular compartments (degranulation). By degranulation, neutrophils exercise influence on nearby cells or bacteria by extracellular release of intragranular proteins (exocytosis), and intensify plasma membrane-related processes, such as chemotaxis and respiratory burst, by translocation of membrane-bound proteins to the surface (upregulation). Ultimately, microorganisms may be killed intracellularly following engulfment (phagocytosis). The thesis presents results of protein-chemical analysis of human neutrophils, based on studies of intact cells and subcellular structures (subcellular fractionation). By fractionation, azurophil granules and specific granules can be disunited from each other and from plasma membrane and secretory vesicles. Only partial separation of plasma membrane and secretory vesicles can be obtained. Subcellular structures are identified by markers, e.g. vitamin B12 binding protein for specific granules, and latent alkaline phosphatase for secretory vesicles. The studies demonstrated tetranectin in neutrophils, localized exclusively in the secretory vesicles. Tetranectin was released by incubation of neutrophils in the presence of weak, inflammatory stimuli and paralleled the upregulation of alkaline phosphatase, but preceded degranulation of specific granules. Alkaline phosphatase has previously been employed as a plasma membrane marker. A novel ELISA for HLA class I antigen was introduced as a new plasma membrane marker. Results obtained by this assay showed upregulation of alkaline phosphatase occurring without a concurrent redistribution of HLA antigen. This indicates that the two proteins are localized in separate compartments. Upregulation of alkaline phosphatase induced by weak stimuli, however, paralleled the translocation of cytochrome b559, anticipated to be the terminal component in the respiratory burst, and known to be localized primarily in the specific granules. The present studies indicate that 15% of cytochrome b is localized in the secretory vesicles. An ELISA was established for quantitation of beta 2-microglobulin, the light chain of HLA class I antigens. The concentration of beta 2-microglobulin in plasma from patients with chronic myeloid leukaemia was found to correlate with the concentration of vitamin B12 binding protein.4+ Measurements in neutrophils demonstrated 65% of the total content of beta 2-microglobulin to be localized in the specific granules, and 20% to be present in secretory vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human neutrophil structure and function with special reference to cytochrome b559 and beta 2-microglobulin. 849 95

All-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells.
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PMID:AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. 860 43

A new sensitive method for the measurement of 1-beta-D-arabinofuranosyl-CTP (ara-CTP), an intracellular active metabolite of 1-beta-D-arabinofuranosylcytosine (ara-C), in human materials in vivo has been established. An acid-soluble fraction containing ara-CTP was extracted from blastic cells by ara-C treatment with trichloroacetic acid (final concentration, 0.3 M) neutralized with an equal volume of cold freon containing 0.5 M tri-n-octylamine. The ara-CTP fraction was separated from the acid -soluble fraction by high-performance liquid chromatography (TSK gel diethylaminoethyl-2 SW column) eluted with 0.05 M phosphate buffer (pH 6.9) and 20% acetonitrile. ara-CTP was lyophilized, dephosphorylated to ara-C by incubation with 10 units alkaline phosphatase for 12 h at 55 degrees C, and measured by RIA using anti-ara-C serum. Recovery through the whole procedure was 92%. In the human chronic myelogenous leukemia cell line K562, the intracellular ara-CTP levels produced when the cells were incubated with ara-c were assayed as above, and they showed a linear increase depending on Ara-C concentrations from 0.01 to 10 microns, demonstrating a very close correlation with the labeled ara CTP levels yielded by cells on incubation with radiolabeled ara-C (r2 = 0.99). The detection limit was 0.1 pmol/5 x 10(6) cells, and a sample amount of only 5 x 10(6) cells was enough for each assay. In the clinical applications, our method proved capable of detecting a wide concentration range of ara-CTP produced when patients were treated with ara-C or its derivatives from very low to intermediate doses. No radiolabeled drug was necessary. The method was very useful for in vivo pharmacodynamic studies of ara-C therapy.
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PMID:A new sensitive method for determination of intracellular 1-beta-D-arabinofuranosylcytosine 5'-triphosphate content in human materials in vivo. 862 Apr 96


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