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)

Bone marrow cells of a 45-year-old female with Philadelphia chromosome (Ph1)-positive, early-phase chronic myelogenous leukemia (CML), who was heterozygous for the glucose-6-phosphate dehydrogenase (G6PD) locus, were pretreated in vitro with 4-hydroperoxycyclophosphamide (4-HC) and tested for G6PD activity in several colony formation assays and for karyotypic abnormalities. All cells within the mixed (CFU-GEMM), the erythroid burst (BFU-E), and the granulocyte-macrophage (CFU-GM) colonies expressed type A and type B G6PD activity and a normal karyotype, whereas untreated cells expressed type A G6PD and the Ph1 chromosome. This reversal of G6PD activity type and the disappearance of the Ph1 chromosome in colonies grown from 4-HC-treated cells indicate that this cytotoxic agent spares a residual normal stem cell population in bone marrow cells of early-phase CML patients. This finding, in turn, suggests a therapeutic approach in CML based on in vitro chemotherapy of autologous bone marrow grafts.
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PMID:In vitro restoration of polyclonal hematopoiesis in a chronic myelogenous leukemia after in vitro treatment with 4-hydroperoxycyclophosphamide. 385 67

Surface antigens were analyzed on normal human marrow and chronic myeloid leukaemic cells using 4 monoclonal mouse anti-human antibodies. The fluorescence-activated cell sorter was used to quantify the binding of each antibody to different subpopulations of cells, and sorted fractions were cultured in agar-medium to assay for granulocyte-macrophage and eosinophil precursors. All cells in the granulocyte series including colony-forming cells bound a similar quantity of an antibody to the human leucocyte common antigen. This antibody did not bind to cells in the erythroid series. A monoclonal antibody to antigen present on brain, lymphocytes and granulocytes (and almost certainly homologous to the W3/13 antigen of the rat) bound to the cells in the order: blast greater than promyelocytes and myelocytes greater than granulocytes. The third monoclonal antibody was directed against a determinant of the leucocyte common antigen present predominantly on B lymphocytes and absent from the myeloid series. The fourth antibody, directed against the human homologue of Thy-1, reacted with less than 1% of marrow cells, none of which appeared to be granulocyte or eosinophil progenitors. The leucocoyte common antigen and the brain-lymphocyte-granulocyte-antigen were also present on colony- and cluster-forming cells from a patient with chronic myeloid leukemia. Using the low angle and wide angle light scatter properties of CML blood cells, 7-fold enrichment was obtained for progenitor cells from chronic myeloid leukaemia. With the monoclonal antibodies up to 4-fold enrichment was obtained.
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PMID:Surface antigens on normal and leukaemic human cells detected by monoclonal antibodies. 616 94

The production of basophils in semisolid agar cultures form normal and chronic myeloid leukemia (CML) committed granulocyte-macrophage precursors was investigated using an original whole-dish staining technique with toluidine blue which produces a specific metachromasia in basophils. As additional proof of the basophilic nature of metachromatic cells, their degranulation after challenge with C5a anaphylotoxin and Synachten was observed. Our studies show that few basophils are produced in cultures form normal bone marrow. CML CFUc produce more basophils, their number being roughly correlated with the degree of basophilia. We observed only clusters composed by a pure basophilic population, while larger aggregates in which basophils could be detected were composed also by other granulocytic cells.
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PMID:Detection of basophils growing in semisolid agar culture. 616 3

We describe an antigen(s) characterized by a heteroantiserum raised in rabbits against mature human granulocytes. This antigen was found on neutrophils, monocytes, platelets, acute and chronic myelocytic leukemia cells and on granulocyte-macrophage progenitor cells grown in agar. It was not found on lymphocytes, eosinophils, erythrocytes, or erythroid progenitor cells. On the basis of tissue distribution and absorption studies, the antigen (tentatively designated the "myelo-monocytic" antigen) is distinct from antigens previously identified on human neutrophils. Restriction of the "myelo-monocytic" antigen to normal and malignant cells of the myelo-monocytic series suggests that it may represent a normal differentiation antigen of the myelo-monocytic lineage.
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PMID:An antigen expressed by cells of the myelo-monocytic lineage. 616 91

The ability to modulate granulocyte-macrophage colony-forming unit (CFU-GM) Ia-antigen expression and response to growth inhibition in vitro was investigated in normals and patients with chronic myeloid leukemia (CML). The hyporesponsiveness of CML CFU-GM to inhibition by prostaglandin E and acidic isoferritins in vitro and their associated diminished capacity for Ia-antigen expression could be reversed following suspension culture of bone marrow cells in the presence of prostaglandin E prior to soft agar culture. Suspension preculture with prostaglandin E for 24 hr resulted in the detection of a population of CFU-GM that were equivalent to normal CFU-GM in both response to inhibition by prostaglandin E and acid isoferritins and in their pattern of Ia-antigen expression. Cytogenetic analysis of the progeny of CFU-GM proliferating in cultures established from marrow cells, cultured directly upon isolation or following suspension culture in the absence or presence of prostaglandin E for 24 hr, indicated that the responding cell population belonged to the Ph1-positive leukemic clone. Antigen detection on these CFU-GM resulted both from Ia-antigen reexpression and the induction of noncycling cells into S-phase with coincident expression of Ia-antigens. These studies provide further evidence for a direct regulatory association between Ia-antigen and control of granulocyte-macrophage progenitor cell proliferation, offer a possible explanation for the disordered regulatory responses observed in patients with CML, and indicate that abnormal growth phenotypes can be modulated, at least in vitro.
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PMID:Restoration of responsiveness of chronic myeloid leukemia granulocyte-macrophage colony-forming cells to growth regulation in vitro following preincubation with prostaglandin E. 657 94

The effects of three S-phase-specific agents, [3H]thymidine, hydroxyurea, and 1-beta-D-arabinofuranosylcytosine, on granulocyte-macrophage colony-forming units (CFU-C) and erythroid progenitor cells (erythroid burst-forming units) (BFU-E) from the bone marrow or peripheral blood obtained from 23 normal individuals and 12 patients with chronic myelogenous leukemia were investigated. CFU-C, regardless of their source, showed comparable degrees of sensitivity to each of the S-phase-specific agents, with perhaps a slightly greater level of sensitivity to [3H]thymidine. In contrast, the sensitivities of chronic myelogenous leukemia and normal marrow BFU-E to the 3 agents were quite different, with essentially all BFU-E being killed by [3H]thymidine, 50 to 70% being killed by 1-beta-D-arabinofuranosylcytosine, and only 15 to 20% being killed by hydroxyurea. BFU-E present in normal peripheral blood were insensitive to [3H]thymidine or hydroxyurea but were sensitive to 1-beta-D-arabinofuranosylcytosine. These studies demonstrated similarities between the CFU-C and BFU-E of CML patients and the CFU-C and BFU-E present in normal bone marrow. On the other hand, the sensitivities of normal peripheral blood progenitor cells to "S-phase-specific" agents differed from that of CML progenitor cells or the progenitor cells present in normal bone marrow. Additionally, these studies have demonstrated the limitations inherent in suicide techniques as methods for estimating the cell cycle characteristics of clonogenic cells.
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PMID:Effects of S-phase-specific agents on granulocyte-macrophage and erythroid progenitor cells obtained from normal individuals and from patients with chronic myelogenous leukemia. 657 19

The studies described compare the subpopulations of granulocyte-macrophage progenitor cells present in normal marrow with those derived from the marrow of patients with Ph1-positive chronic myelogenous leukemia (CML). The subpopulations were separated on the basis of size by velocity sedimentation and measured for their proliferative capacity by the colony formation technique. A pattern of development of colonies in the individual fractions was obtained by assaying the absolute number of colonies present at time intervals from 3 to 21 days. The number of colonies present at 3 days was taken as 100%, and the percentage of increase or decrease from this value was determined on subsequent days. In the fractions containing the most rapidly sedimenting large cells, the pattern of development of colonies derived from normal and CML marrow was similar. The CML colony-forming units in culture (CFU-C) began to show a deviation from the normal CFU-C pattern of development in the fractions containing CFU-C intermediate in size, and this deviation became progressively more pronounced in the slowest sedimenting small cell fractions. In these latter fractions, the CFU-C derived from CML marrow decreased in number at a rate similar to those arising from the more rapidly sedimenting fractions. This is in contrast to CFU-C derived from normal marrow, which increased in number in the more slowly sedimenting fractions and in the intermediate fractions, remained constant in number, or decreased at a rate slower than those arising from the more rapidly sedimenting fractions. The most likely explanation for these findings is accelerated maturation of the early small granulocyte-macrophage progenitor cells in CML so that these cells show the same limited proliferative capacity as do the later larger progenitor cells.
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PMID:Proliferative potential of subpopulations of granulocyte-macrophage progenitor cells in normal subjects and chronic myelogenous leukemia patients. 657 38

As part of an attempt to develop and test potential in vitro measures of busulfan sensitivity of patients with chronic myelogenous leukemia (CML) in chronic phase, we compared the busulfan sensitivity of granulocyte-macrophage (CFU-C) and early erythroid progenitor cells (BFU-E) in the bone marrow (BM) and peripheral blood (PB) specimens obtained from ten normal individuals and from 13 patients with CML. CFU-C in the normal BM and in both the BM and PB of CML patients showed comparable degrees of sensitivity to busulfan. BFU-E, regardless of source, showed similar degrees of sensitivity to busulfan, except that normal PB BFU-E were less sensitive than were PB BFU-E of CML patients. CFU-C were more resistant to busulfan than BFU-E. The sensitivity of BM CFU-C and BFU-E of CML patients reflected that of PB CFU-C and BFU-E, respectively, and the sensitivity of BM and PB CFU-C of CML patients reflected that of BM and PB BFU-E, respectively. When the CML patients were ranked according to sensitivity to busulfan, the order of sensitivity of BM CFU-C and BFU-E paralleled that of PB CFU-C and BFU-E, respectively, and the order of sensitivity of BM and PB CFU-C paralleled that of BM and PB BFU-E, respectively. These results suggest that any of the four progenitor cells, BM CFU-C, BM BFU-E, PB CFU-C, and PB BFU-E, can be used to investigate the relative busulfan sensitivity of the hemopoietic progenitor cells of different CML patients.
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PMID:In vitro busulfan sensitivity of granulocyte-macrophage and erythroid progenitor cells in patients with chronic myelogenous leukemia. 658 66

In the process of evaluating roles for purified preparations of lactoferrin, transferrin and acidic isoferritins in the regulation of myelopoiesis, it was found that: (1) values reported for lactoferrin in the serum and plasma of normal donors are in most cases an over-estimation, (2) lactoferrin suppresses the production/release of granulocyte-macrophage colony stimulatory factors (GM-CSF) from monocytes in the absence of T-lymphocytes and also suppresses the production/release of acidic isoferritin-inhibitory activity from monocytes, (3) lactoferrin, transferrin and acidic isoferritins act on their specific target cells which express Ia-like antigens, (4) lactoferrin and transferrin act in vivo to suppress rebound myelopoiesis in mice recovering from sublethal dosages of Cytoxan, with preliminary observations suggesting that lactoferrin has a greater apparent effect on the bone marrow and transferrin has a greater apparent effect on the spleen, (5) active lactoferrin derives from Fc receptor positive subpopulations of PMN from patients with CML as well as from normal donors, but the percentage of Fc receptor containing PMN is lower in CML, as is the amount of active lactoferrin found in their PMN, and (6) lactoferrin, transferrin and acidic isoferritins suppress the colony formation of U937 clonogenic cells, with lactoferrin and transferrin decreasing the release of growth factors from U937 cells which are needed to stimulate U937 colony formation, and lactoferrin and acidic isoferritins suppress the colony formation of WEHI-3 cells, with lactoferrin decreasing the release of growth factors from WEHI-3 cells which are needed to stimulate WEHI-3 colony formation. Speculation on the potential usefulness of these iron binding glycoproteins to control of disease progression is given in the discussion.
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PMID:Lactoferrin, transferrin and acidic isoferritins: regulatory molecules with potential therapeutic value in leukemia. 660 37

The capacity of fetal bone marrow to form stromal cell colonies, granulocyte-macrophage colonies, stromal cell monolayers and to produce granulocyte-macrophage colony stimulating activity from these monolayers was evaluated in comparison to adult bone marrow. Granulocyte-macrophage colony formation on routine feeder layers was approximately equal in both cases. The fetal bone marrow colonies were larger in size than those from adult precursors. There were at least ten times more stromal cell precursors in fetal bone marrow than in adult bone marrow. The fetal bone marrow stromal cell monolayer formed within 7-12 days whereas adult stromal monolayer formation required 3-4 weeks. Fetal bone marrow stromal cell monolayer produced granulocyte-macrophage colony-stimulating activity (GM-CSA) effective only for fetal GM precursors, whereas adult bone marrow produces GM-CSA effective for fetal and adult normal and CML bone marrow.
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PMID:The properties of human fetal bone marrow stromal and hemopoietic cells. 666 7


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