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 surface membrane glycoproteins of pseudo-Pelger granulocytes in six patients suffering from chronic myeloid leukaemia (CML). We studied the functional and immunochemical activities of five monoclonal antibodies (MoAb) minimally reactive with integrin familial antigens of pseudo-Pelger granulocytes. The study conducted with cytofluorimetric and immunological alkaline phosphatase anti-alkaline phosphatase (APAAP) analysis showed a decreased expression of CD11b/CD18 detected by antibodies OKM1, 60.1 and 60.3 (P less than 0.001). Lymphocyte function associated antigen (LFA-1) was expressed in normal amounts in pseudo-Pelger granulocytes. There was decreased expression of CD11b/CD18 in pseudo-Pelger granulocytes with respect to controls (P less than 0.001) after stimulation with formyl-met-leu-phe (FMLP). We conclude that acquired pseudo-Pelger granulocyte dysfunction may be correlated to decrease of surface glycoprotein expression of CD11b/CD18.
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PMID:Surface expression of CD11b/CD18 of pseudo-Pelger granulocytes in chronic myeloid leukaemia. 198 28

We report on a 69-year-old man who developed Ph-positive CML 6 years after the onset of B-cell CLL. When CML was diagnosed, both malignant cell populations were detected in bone marrow and peripheral blood. Peripheral leukocytes were fractionated by Ficoll-Hypaque density gradient, and cytogenetic and molecular studies were performed on mononuclear cell and granulocyte-enriched populations. Mononuclear cells were stimulated with either PHA or PWM. In PHA-treated cultures 76% of the metaphases were Ph-negative, while after PWM stimulation 87% were Ph-positive. A bcr rearrangement was observed in DNA from the granulocyte-enriched fraction, but not in mononuclear cells. On the contrary the IgH locus resulted in monoclonally rearranged DNA, only in peripheral blood mononuclear cells. These results indicate that the two neoplastic populations originated independently.
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PMID:Chronic myelogenous leukemia in the course of chronic lymphocytic leukemia: evidence for an independent clonal origin. 203 Jun 9

Reactive leukocytosis has been reported in patients with non-Hodgkin's lymphoma of different histologic types. On the other hand, the blastic crisis of chronic myelocytic leukemia (CML) can sometimes be localized outside the bone marrow and simulate lymphoma, particularly when the blasts are of lymphoid lineage and the blastic crisis is the presenting feature of the disease. We report two patients in whom the differential diagnosis between lymphoblastic lymphoma with reactive leukocytosis and blastic crisis of CML outside the bone marrow was raised. They were two males aged 32 and 22 years, respectively, with lymphadenopathy (and one with splenomegaly), who were initially diagnosed of T lymphoblastic lymphoma. In both cases, leukocytosis was detected with myelemia and dysgranulopoiesis in the onset in one of them and when lymphadenopathy reappeared after remission in the other one. In addition, one patient had marked eosinophilia. In the bone marrow there was marked granulopoietic hyperplasia, with a reduction of fatty cells, and the granulocyte alkaline phosphatase index was reduced. However, the cytogenetic study did not disclose the existence of Philadelphia (Ph) chromosome, and bcr/abl molecular rearrangement was also not observed in the molecular study of both cases. We discuss the basic aspects of differential diagnosis between T lymphoblastic lymphoma with leukemoid reaction and T lymphoid lymphadenopathic blastic crisis of Ph-negative, bcr/abl-negative CML.
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PMID:[T lymphoblastic leukemia with leukemoid reaction or the extramedullary blast crisis of Philadelphia chromosome-negative chronic myeloid leukemia? Comments apropos 2 cases]. 209 54

Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML.
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PMID:Elevated white blood cell synthesis of leukotriene C4 in chronic myelogenous leukaemia but not in polycythaemia vera. 211 Apr 64

Study of growth factor RNA levels in the stromal cells derived from the adherent layer of long-term bone marrow culture demonstrated constitutive expression of transforming growth factor beta 1 (TGF-beta 1) and macrophage colony-stimulating factor. These cells did not express granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interleukin (IL) 1 alpha, IL-1 beta, IL-3, and IL-6. However, granulocyte colony-stimulating factor expression could be induced by recombinant human IL-1 beta; while IL-6 could be induced by both IL-1 beta and tumor necrosis factor-alpha. No differences could be detected between adherent layers established from normal and benign phase Ph1 chronic myelogenous leukemia bone marrow. The uninduced expression of TGF-beta 1, a potent hematopoietic cell growth inhibitor, suggests that stromal cells play an inherent role in regulating the proliferation of adjacent bone marrow hematopoietic progenitor cells. However, a defect in stromal TGF-beta 1 production cannot account for the profoundly expanded myeloid compartment in chronic phase chronic myelogenous leukemia. In contrast to the constitutive expression of TGF-beta 1 and macrophage colony-stimulating factor, hematopoietic growth factors are only expressed following a proper stimulation.
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PMID:Constitutive and induced expression of growth factors in normal and chronic phase chronic myelogenous leukemia Ph1 bone marrow stroma. 220 22

In the present study we have characterized the cytotoxicity and DNA damage induced by hepsulfam and busulfan in cells isolated from both chronic myelogenous leukemia (CML) patients and normal donors. hepsulfam inhibited colony-forming units-granulocyte, macrophage to a greater extent than busulfan in peripheral blood cells (PBCs) isolated from CML patients. Normal PBCs were equally sensitive to both agents and were more sensitive than the cells isolated from CML patients. Hepsulfam induced DNA interstrand cross-links in PBCs and bone marrow from both CML and normal volunteers, whereas busulfan produced few or no DNA interstrand cross-links. In addition, hepsulfam induced higher levels of DNA interstrand cross-linking than busulfam in three samples isolated from CML patients in blast crisis. Busulfan did however cause a small number of DNA strand breaks to be formed in human cells. Both agents produced similar levels of DNA-protein cross-links in PBCs from CML patients. These results suggest that the mechanism of DNA reactivity of hepsulfam and busulfan differ and that hepsulfam may prove useful in the treatment of CML.
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PMID:In vitro studies on the mechanism of action of hepsulfam in chronic myelogenous leukemia patients. 225 5

To examine the role of DNA methylation in breakpoint location of chromosomal translocation, HpaII sites in and flanking the M-bcr on chromosome 22 were mapped in DNA from blood granulocytes and lymphocytes, bone marrow cells, thymic tissue, and spermatozoa from normal individuals. Allelic HpaII sites were identified clustered in a 600-base pair genomic area of the M-bcr. Bone marrow cells and blood granulocyte DNA showed identical allelic patterns. Thymic tissue and blood lymphocytes showed identical allelic patterns distinct from bone marrow cells and blood granulocytes. Spermatozoa showed a third methylation pattern. In all individuals, the HpaII sites were present within the BamHI/BglII fragment of the M-bcr, the same area associated with high breakpoint frequency in chronic myelogenous leukemia (CML). Three of 15 patients with chronic phase CML showed fully methylated rearranged BglII/BglII M-bcr restriction fragments not seen in normal bone marrow cells. These methylation patterns of the M-bcr may be important in CML breakpoint location and may be a marker for tissue differentiation.
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PMID:Presence of cell lineage-specific hypomethylated sites in the major breakpoint cluster region. 237 63

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C, to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-induced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fms and interleukin-1 beta RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.
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PMID:Differentiation and growth modulation of chronic myelogenous leukemia cells by bryostatin. 238 56

The major initial clinical, hematological and cytogenetical features of a series of 80 patients with blastic crisis (BC) in chronic myelocytic leukemia with positive Philadelphia chromosome (Ph) were evaluated, and also were their outcome and response to therapy. Mean age of patients was 45 years (SD: 14.3). Ten patients fulfilled the criteria for initial BC, and 14 had extramedullary blastic infiltration. In one third there was an acceleration phase before the development of BC. The mean leukocyte count was 69 (SD 75) X 10(9)/l. In 40% there was anemia with hemoglobin less than 90 g/l, and 37.5% had thrombopenia with less than 100 X 10(9) cells/l. In most patients, serum lactic dehydrogenase activity was increased, and in one fourth the index of granulocyte alkaline phosphatase was high. In 9 patients, blast cells had a lymphoid phenotype and in 47 (59%) cytogenetic abnormalities in addition to Ph chromosome were found, usually consisting of 8 trisomy, duplication of Ph chromosome, and the presence of a 17q isochromosome. The median survival of the series was 4.8 months. When analyzed as a time-dependent variable, the achievement of a favorable therapeutic response (found in 26% of patients) was associated with a longer survival.
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PMID:[Blast crisis of chronic myeloid leukemia with positive Philadelphia chromosome: course and clinico-hematologic profile in 80 patients]. 238 91

The possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
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PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48


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