Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolerance was induced against cytotoxic target determinants coded for by genes of the I region. Neonatal recipients were immunized with high doses of cells from an I region incompatible donor. Nonreactivity in adult life did not reflect extensive donor cell chimerism, since the great majority of cells in spleens of animals rendered tolerant were of host phenotype. Although specific nonresponsiveness in CML could be induced by these protocols, the MLC proliferative response was in most cases still present alghough very much decreased. In only a very occasional animal was complete nonreactivity in MLC seen. The nonresponse in CML was paralleled by acceptance of thyroid allografts as measured by radioactive iodine incorporation and morphological studies.
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PMID:Tolerance induction to H-2 central region target antigens: in vivo/in vitro correlations. 14 1

The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation.
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PMID:Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia. 192 49

Prognostic models for acute myeloid and lymphoid leukemias are presented that demonstrate that cell kinetic quiescence in acute leukemia is associated with poor response to chemotherapy, short remission duration, and survival. Recruitment of cells into the cell cycle should therefore enhance cytotoxic effects of cell cycle - specific chemotherapeutic agents. We previously demonstrated recruitment of myeloid leukemic cells by cytokines. We have now investigated whether recruitment can be used to increase cell killing by cytosine arabinoside (Ara-C). Blast cells from 16 acute leukemias were stimulated with cytokines as follows: 13 acute myeloid leukemias (AML) and 3 chronic myeloid leukemia (CML) in blastic phase (1 lymphoid, 2 myeloid) were treated with recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony stimulating factor (rhG-CSF, AMGEN, 500 U/ml each), and recombinant human interleukin-3 (rhIL-3, IMMUNEX, 20 ng/ml), alone and in combination. After 48 h, at the time of maximal DNA synthesis, Ara-C (10(-3) M) was added and cell counts, cytokinetics (DNA/RNA, DNA/bromodeoxyuridine and DNA/Ki67 flow cytometry), and cell viability/clonogenicity (fluorescein diacetate/propidium iodide exclusion flow cytometry) were investigated. In all 13 cases of AML recruitment was found; in 6 of these cases over a three fold increase in S phase (P = 0.008) and a significant (P = 0.004) depletion of G0 was demonstrated. In 9 of 13 patients with AML, the effect of Ara-C was investigated, and in 3 of 5 patients with over three fold increase in S phase, Ara-C toxicity was enhanced. None of the patients with less than a three fold increase in S phase and no demonstrable recruitment from G0 had increased Ara-C cytotoxicity. Ara-C cytoreduction was paralled by reduction in clonogenicity as demonstrated by fluorescein diacetate/propidium iodide (FDA/PI) flow cytometry. Four samples of acute lymphoblastic leukemia (ALL) were treated with low molecular weight B-cell growth factor (15 kDa) and recruitment of aneuploid cells from G0 to G1 was found in all patients (from 19.3% to 84.9%). These results indicate that recruitment of leukemic cells is inducible by cytokines and that the cytotoxicity of cell cycle-specific drugs such as Ara-C can be increased. This concept is presently being tested in vivo.
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PMID:Colony-stimulating factors (rhG-CSF, rhGM-CSF, rhIL-3, and BCGF) recruit myeloblastic and lymphoblastic leukemic cells and enhance the cytotoxic effects of cytosine-arabinoside. 232 74

Evaluation of double-stranded RNA by flow cytometric analysis is an important parameter for discriminating quantitatively between human tumoral and normal cells. We studied double-stranded RNA (ds-RNA) measurements using propidium-iodide after DNase treatment in bone marrow and in peripheral blood cells from patients with acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma. The highest incidence of ds-RNA excess (greater than 30%) was observed in patients with acute leukemia (75%), while those displaying it in complete remission phase were 20-25% and in relapse about 80%. A high incidence was also noted in patients with chronic myeloid leukemia in blastic crisis (100%) and in patients with multiple myeloma with heavy tumor stage myeloma (78%). We never observed an elevated ds-RNA excess in the control group, formed by normal peripheral blood lymphocytes. Indeed the specificity of this tumor marker is attested to not only by its high levels in various hematologic malignancies, but also by its absence in normal cells. Hence the importance of its clinical implications in malignant hematologic diseases is confirmed.
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PMID:Double-stranded RNA excess in hematologic diseases: clinical implications. 263 84

The activity of P-32 removed during leukapheresis of a patient previously administered P-32 for therapy of chronic myelogenous leukemia (CML) was determined. The bremsstrahlung produced by P-32 beta rays in the pheresis bags allowed the quantitation of radioactivity by well counting in a sodium iodide detector and by a gamma camera. Bremsstrahlung counting demonstrated that leukapheresis removes such a small amount of radioactivity that the therapeutic effect of a previously administered P-32 dose was still valid. Bremsstrahlung counting offers advantages to a Nuclear Medicine Department over the conventional use of a liquid scintillation counter to detect P-32 beta rays in that it is simpler and more readily available.
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PMID:Quantification of P-32 removed during leukapheresis by bremsstrahlung counting. 658 32

Cell kinetics were studied in human leukemia (acute leukemia, chronic myelocytic leukemia and other myelocytic malignancies) and in mouse leukemia (L 1210 cells). Flow cytometry method was employed for the analysis of DNA distribution of cells stained with propidium iodide, using a cytofluorograf (System 50, Ortho Instruments). The DNA per cell frequency distribution histograms (DNA histogram) in normal human lymphocytes from peripheral blood showed one main peak of diploid, which corresponded to the DNA from cells in G1 phase of the cell cycle, and other small portions, which corresponded to the DNA from cells in S, G2 and M compartments (S + G2 + M). The percentage of the number of cells in the S + G2 + M phase to the total cells from normal controls was 2.1%. In the case of untreated acute myelocytic leukemia (AML), the percentages of cells in the S + G2 + M phase from peripheral blood and bone marrow were 2.4% and 7.1%, respectively. In bone marrow from treated AML, the percentage of cells in the S + G2 + M phase increased to 14.8%. In the case of untreated acute lymphocytic leukemia, the percentages of the S + G2 + M phase from peripheral blood and bone marrow were 1.9% and 7.1%, respectively. After the treatment of chronic myelocytic leukemia, the percentages of the S + G2 + M phase in peripheral blood and bone marrow were 5.8% and 12.2%, respectively. The DNA histogram in untreated L 1210 cells showed two peaks. One of the peak was consisted of the DNA from cells in G1 phase and another was from cells in the S + G2 + M phase. The proportion of the S + G2 + M phase in the L 1210 cells treated with antitumor drugs significantly increased compared to the untreated cells. The findings indicate that the increase in the proportion of the S + G2 + M phase in the cells from treated human leukemia was a result of the therapeutic effects of antitumor drugs. The study of cell kinetics may provide benefits to know the effect of antitumor drugs during the treatment of human leukemia.
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PMID:[Studies on cell kinetics in leukemia using flow cytometry]. 715 63

Steel factor (SF) acts synergistically with other hematopoietic growth factors to support the proliferation of progenitor cells in a variety of culture systems. To determine whether SF alone could directly stimulate proliferation of early hematopoietic progenitor cells, isolated CD34+ cells from adult bone marrow and umbilical cord blood were studied in a short-term suspension culture in serum-free medium. Numbers of CD34+ and proliferating cells were quantified by flow cytometry; proliferation was assessed by simultaneous measurement of expression of the nuclear antigen Ki67 and DNA content (propidium iodide [PI]). In the absence of growth factors, the numbers of CD34+ and cycling cells declined over 2 days. Cells cultured in the presence of SF alone maintained the number of CD34+ and cycling cells at levels equal to the starting population. Withdrawal of growth factors led to a dramatic decrease in the number of cells in G1. Compared to cells grown in the absence of growth factors, cells grown in the presence of SF had significantly higher numbers of CD34+ and cycling cells (mean fold increase = 1.3 and 2; p < 0.05 and 0.01, respectively). SF increased the numbers of cells in both G1 and later phases of the cell cycle. Addition of interleukin-3 (IL-3) to SF led to further significant increases in CD34+ and cycling cells. The effects of SF could not be attributed to inhibition of apoptosis. CD34+ cells isolated from peripheral blood (PB) from patients with chronic myelogenous leukemia (CML) displayed similar characteristics. As assessed by binding of phycoerythrin (PE)-labeled ligand and flow cytometry, c-kit was expressed on 65 +/- 6% of isolated CD34+ cells and was detected on HLA-DRlow, CD38low, and Thy1+ subsets, as well as on more mature progenitor cells. Thus, while the effects of SF are most marked in combination with other growth factors, SF appears to bind to and directly maintain the active cell-cycle characteristics of isolated CD34+ cells.
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PMID:Steel factor supports the cycling of isolated human CD34+ cells in the absence of other growth factors. 753 83

Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR-ABL expression is a mechanism that might contribute to clonal expansion in chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing radiation and many chemotherapeutic agents can occur by the apoptotic pathway, inhibition of apoptosis would be expected to confer a relative resistance to these treatments. Similarly, cells deprived of growth factors in vitro die by apoptosis, and inhibition of apoptosis would therefore be expected to allow cells to survive better in growth factor-deprived conditions. We found that the survival of normal and CML myeloid progenitors was the same after in vitro incubation in deprived conditions and after treatment with X-irradiation or glucocorticoids. We also found that mature cells in colonies produced by CML progenitors (CFU-GM) did not survive better than those produced by normal progenitor cells. Flow cytometric analysis of propidium iodide-stained cells provided a direct indication that the degree of apoptosis may correspond to the degree of deprivation. These results suggest that inhibition of apoptosis may not be the primary mechanism whereby BCR-ABL influences the expansion of the malignant clone in CML.
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PMID:Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids. 854 80

Leukaemia is an uncommon late complication of exposure to the ionizing radiation of radioactive iodine (131I). Most cases reported have been of acute leukaemias developing after high doses of 131I. Only a few cases of chronic myeloid leukaemia (CML) have been reported in this setting to date. We report two new cases of CML after low dose radioactive iodine and review the literature. We present an analysis of the minimal relative risk of CML developing in thyroid cancer patients treated with 131I in Israel. Two male patients, 35 and 51 years old, developed CML following low dose 131I therapy for metastatic mixed papillary and follicular carcinoma of the thyroid. Both had undergone thyroidectomy and neck dissection and thyroid ablation with 131I (total dose: 56 and 130 mCi respectively). Four and 10 years later, respectively, a leucocytosis was noticed with typical blood smears, and CML was diagnosed either by Philadelphia translocation or bcr-abl gene rearrangement. Thyroid cancer at that time was in remission. Estimated minimal relative risk of CML after 131I therapy where the population considered at risk comprised all thyroid cancer patients detected during the years 1981-1991 in Israel was 8.95 (95% confidence limits 2.26-35.16). Literature review disclosed five additional similar cases. The mean radioiodine dose given to the seven CML patients was 11416MBq (range 1134-32130 MBq), considerably lower than the dose given to patients reported in the literature who subsequently developed acute leukaemias (mean 34965, range 3856-54810 MBq). We suggest that CML is a potential complication of low dose 131I therapy given for thyroid carcinoma even at the lower end of the dose range used for this indication. Leucocytosis appearing in these patients should raise the suspicion of secondary CML.
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PMID:Chronic myeloid leukaemia following 131I treatment for thyroid carcinoma: a report of two cases and review of the literature. 854 52

Phenotype and cell cycle distribution in peripheral blood and bone marrow mononucleated cells was studied in patients with different leukemias: T-ALL, AML, CLL, CML and plasmocytoma. DNA flow cytometry with propidium iodide fluorescence was used. Differences in cell cycle between mononucleated cells from T-ALL and CML patients on one hand and normal controls on the other were seen in peripheral blood but not in bone marrow specimens. Patients with AML, CLL and plasmocytoma showed a cell cycle distribution of mononucleated cells similar to normal controls. DNA content analysis in some leukemias were discussed.
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PMID:Analysis of the phenotype and cellular DNA content in some leukemias by flow cytometry. 859 78


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