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 investigated the in vitro action of recombinant tumor necrosis factor alpha (TNF) on the clonal growth of normal and malignant myeloid cells. Clonogenic cells from six of nine myeloid leukemia cell lines were very sensitive to the effects of TNF with 50% of the colonies inhibited (ED50) by concentrations of TNF that ranged between 6 and 150 U/mL. A decrease in DNA, RNA, and protein synthesis and in cloning efficiency occurred within three hours of exposure of HL-60 promyelocytes to TNF. The TNF in combination with recombinant interferons produced an additive or synergistic inhibition of colony formation of HL-60 and THP-1 myelomonoblasts. Normal human CFU-GM are sensitive to TNF (ED50 between 100 and 50,000 U/mL), but their sensitivity to TNF depends on the source of colony stimulating factor (CSF) with T lymphocyte derived GM-CSF (recombinant or natural) partially protecting the CFU-GM from the suppression exerted by TNF (and interferons). In eight of 15 cases the clonogenic myeloid leukemia cells from patients with acute or chronic myeloid leukemia were more sensitive than normal CFU-GM using GM-CSF as a source of colony stimulating activity. Further studies showed that the action of TNF on myeloid leukemia cells probably can be only partially explained by differentiation. Our finding of a possible selective cytotoxicity to leukemic clonogenic cells by TNF suggests that TNF may have value in the therapy of some patients with myeloid leukemia.
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PMID:In vitro action of tumor necrosis factor on myeloid leukemia cells. 243 41

Respiratory burst develops in myeloid blast cells if they differentiate functionally along the monocytic or granulocytic lineage. Using the nitroblue tetrazolium (NBT) assay we studied the effects of recombinant human granulocyte/macrophage colony stimulating factor (rhuGM-CSF), rhuG-CSF and rhuM-CSF on development of respiratory burst activity in primary blast cells from patients with myeloid leukemia. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (AML, n = 13) or myeloid-blast crisis (myBC) of chronic myeloid leukemia (CML, n = 5) it was found that the percentage of NBT positive cells was increased by at least 20% as compared to control cultures by rhuGM-CSF in 6/17 cases, by rhuG-CSF in 7/17 cases and by rhuM-CSF in 0/16 cases, representing in 'responders' a mean increase of 267% and 270% in the absolute number of NBT positive cells by rhuGM-CSF and rhuG-CSF, respectively. Morphological examination of cultured cells from 'responders', as compared to controls, showed decreased blast cell content but generally no evidence of terminal differentiation. The demonstration of Auer rods in NBT positive cells indicates that respiratory burst developed in a leukemic clone. These findings may be of physiological, pathophysiological and clinical relevance.
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PMID:Recombinant human colony stimulating factor-granulocyte/macrophage and -granulocyte, but not macrophage induce the development of a respiratory burst in primary human myeloid leukemic cells in vitro. 247 89

A Phase II study of recombinant granulocyte colony-stimulating factor (G-CSF) in allogeneic bone marrow transplantation (BMT) was performed. The recovery of leukocytes and neutrophils was markedly accelerated in G-CSF-administered recipients. The days to WBC count greater than 1,000/microliters (11.5 +/- 1.9) and the days to neutrophil count greater than 500/microliters (11.5 +/- 1.4) were significantly shorter than those of the monocyte-CSF (M-CSF) and CSF(-) groups. In the G-CSF group the WBC count at nadir was higher than in other groups, and neutrophil recovery preceded monocyte recovery. After the discontinuation of G-CSF, the WBC count first decreased for a few days and then increased again slowly. The short duration of leukopenia brought about a reduction in the number of febrile (greater than 38 degrees C) days which, until day 30, were 1.8 +/- 1.9 in the G-CSF group, also significantly shorter than in others. Acute graft-versus-host disease (greater than grade II) appeared in two of eight patients from the G-CSF group, this incidence being comparable to those found in the other groups. A side effect of G-CSF-mild bone pain-was observed in one patient, but it was tolerable. Six of eight patients in the G-CSF group survived for between five and 13 months after BMT with a Karnofsky score greater than 90%. No relapses were observed in the six, including one patient with chronic myelogenous leukemia and two with acute non-lymphoblastic leukemia. To determine the final influence of G-CSF on myeloid leukemia, further long-term follow-up studies are needed. G-CSF was well tolerated and seemed promising against allogeneic BMT.
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PMID:Granulocyte colony-stimulating factor in allogeneic bone marrow transplantation. 248 58

The therapeutic potential of recombinant interferon gamma (IFN gamma) alone or in combination with two cytotoxic drugs - 5-fluorouracil (5-FU) and cytosine arabinoside (Ara-C) - was studied in vitro on two myeloid leukemia systems: HL60 promyelocytic cell line and chronic granulocytic leukemia (CGL) progenitor cells. When applied individually, IFN gamma and the drugs inhibited in a dose-dependent manner HL60 cell colony formation in semisolid culture. Moreover, IFN gamma or the cytotoxic drugs dose-dependently reduced the colony formation of CGL progenitor cell in agar. When added in combination, IFN gamma potentiated synergistically the inhibitory action of 5-FU in both systems. The most pronounced potentiation was detected at concentrations of 0.5 microgram/ml 5-FU and 50 U/ml IFN gamma. On the contrary, the antiproliferative effect of Ara-C was enhanced only subadditively when combined with IFN gamma. In view of the present findings, which are supported by new evidence from the literature, the use of 5-FU in leukemia should be reconsidered. The results further imply the potential value of combined treatment of 5-FU and IFN gamma in leukemia.
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PMID:New combination of 5-fluorouracil and interferon-gamma effective against human myeloid leukemia in vitro. 251 May 79

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.
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PMID:A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20. 251 73

The myeloproliferative disorders (MPD) are a domain in which the bone marrow biopsy (BMB) greatly proved its utility. We have studied the histology of the bone marrow (BM) in all the four entities of MPD: chronic myeloid leukemia (CML) with its subtype, chronic megakaryocytic granulocytic myelosis (CMGM), polycythemia vera (PV), hemorrhagic thrombocythemia (HT) and myeloid metaplasia with myelofibrosis (MMM). The work presents in short some of the clinical and hematologic characters of MPD with special stress upon the histologic modifications of BM, either specific or common to all MPD entities, underlying also the criteria for differential diagnosis.
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PMID:Bone marrow biopsy (BMB). II. Bone marrow biopsy in myeloproliferative disorders. 252 29

We examined activities of procoagulant and fibrinolysis in homogenate of leukemic cells. Procoagulant activity (PCA) was increased in patients with acute myelocytic leukemia (AML) and acute promyelocytic leukemia (APL), but it was significantly decreased in patients with chronic myelocytic leukemia (CML) and adult T cell leukemia. In CML, PCA was increased in the blastic phase. Plasminogen activator activity (PLGAA) was also increased in patients with AML, APL and acute lymphocytic leukemia (ALL) associated with disseminated intravascular coagulation (DIC). Elastase-like activity, trypsin-like activity and chymotrypsin-like activity (CTLA) were increased in those with myelocytic leukemia, but they were low in those with lymphocytic leukemia. PCA, PLGAA and CTLA were significantly higher in patients with DIC than in those without DIC. Measurement of procoagulant and fibrinolytic activity in leukemic cells homogenate may be useful not only for studying hemostatic abnormalities but also for classification of leukemic cells.
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PMID:[Activity of procoagulant and fibrinolysis in homogenate of leukemic cells]. 259 44

Previous studies suggest that malignant cells from some patients with myeloid leukemias produce colony-stimulating factors (CSFs) that can function as autocrine growth factors in vitro. We have examined the roles of interleukin-6 (IL-6) and granulocyte-macrophage CSF (GM-CSF) in the proliferation of myeloid leukemia cells. IL-6 activity was assessed in conditioned medium (CM) from myeloid leukemia cell cultures or cell lysates using IL-6-dependent KD83 and 7TD1 murine cell lines. Media conditioned by cells from patients with chronic myelomonocytic leukemia (CMMoL), but not by normal monocytes, chronic myelogenous leukemia (CML), or acute myelogenous leukemia (AML) cells, contained substantial levels (50 to 1,000 U/10(6) cells) of IL-6. The IL-6 content of CM correlated directly with donor peripheral blood WBC count. CM from two of five CMMoL samples also contained greater than 350 pg/mL GM-CSF. Moreover, CMMoL cells spontaneously formed colonies in semisolid medium. CMMoL colony formation could be partially inhibited by antibodies to IL-6 or GM-CSF, whereas combination of these antibodies gave additive, and nearly complete (greater than 93%), inhibition of spontaneous colony formation. Cell lysates from uncultured CMMoL cells from one patient contained abundant GM-CSF protein but no detectable IL-6. These data suggest that IL-6 and GM-CSF act in vitro as autocrine growth factors for CMMoL cells, and that CMMoL cells in vivo may represent a GM-CSF-dependent autocrine growth system.
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PMID:Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells. 267 12

Suppression of the green fluorescence of acridine orange by 5-bromodeoxyuridine incorporation into cellular DNA was measured by flow cytometry. Bone marrow cells from normal volunteers and patients with chronic myelogenous leukemia acute lymphocytic leukemia acute myelogenous leukemia and multiple myeloma were incubated with BUdR in vitro. By 24 h acridine orange stained cycling cells that had synthesized DNA in the presence of BUdR were differentiated from quiescent cells as a second peak with quenched green fluorescence (DNA). After 72 h in culture 11-65% of the G0/G1 cells from normal bone marrows and bone marrows with myeloid leukemia were identified as cycling in culture by the presence of a second peak with quenched green fluorescence. A greater percentage of cells with BUdR quenched AO fluorescence was associated of acridine orange was higher in the cycling cells that had synthesized DNA in the presence of BUdR than in the non-cycling G0/G1 cells. In one patient with AML there was quenching of the DNA fluorescence of the aneuploid population but not the diploid population indicating that the aneuploid leukemia cells were proliferating. In contrast in patients with multiple myeloma, the quenched fluorescence of the diploid cell population and not the aneuploid cells, indicated that the diploid cells were proliferating. The cells from patients with untreated ALL failed to proliferation prohibiting an in vivo assessment of growth. Although measurements of proliferation obtained by this method are clearly influenced by the cell's adaptation to culture, measurement of BUdR quenching of acridine orange fluorescence is technically feasible and can identify and allow characterization of the cycling population of cells.
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PMID:5-bromodeoxyuridine (BUdR) quenching of acridine orange fluorescence distinguishes cycling and non-cycling normal and malignant bone marrow cells in vitro. 279 84

Herbimycin A, a benzoquinonoid ansamycin antibiotic, is found to reduce intracellular phosphorylation by tyrosine protein kinase. The human chronic myelogenous leukemia cell line K562 expresses a structurally altered c-abl protein with tyrosine kinase activity. When K562 cells are induced to undergo erythroid differentiation by hemin, reduction in the intracellular level of tyrosine phosphorylation occurs. In order to understand the relationship between induction of differentiation and reduction of tyrosine phosphorylation by the c-abl gene product, the effect that herbimycin A, a selective inhibitor of intracellular tyrosine kinase activity, exerts on the differentiation of K562 cells was examined. Reduction of tyrosine phosphorylation in K562 cells by herbimycin A was observed within 1 h. Noncytotoxic concentrations of herbimycin A induced erythroid differentiation of K562 cells but not of murine erythroleukemia 745A cells. The other human myeloid leukemia cell lines (HL-60, THP-1, and U937) tested were not induced to undergo cell differentiation by this antibiotic. Herbimycin A and the other well-known inducers such as hemin, butyric acid, Adriamycin, and 1-beta-D-arabinofuranosylcytosine had additive or more than additive effects on induction of erythroid differentiation of K562 cells. With respect to inhibition of cell growth, the sensitivity of K562 cells to herbimycin A was highest in the human leukemia cell lines we tested. Noncytotoxic concentrations of herbimycin enhanced the antiproliferative effect of Adriamycin or 1-beta-D-arabinofuranosylcytosine on K562 cells. Combination therapy with herbimycin A and its derivatives may be considered for use in the treatment of some types of leukemia where tyrosine kinase activities are implicated as determinants of the oncogenic state.
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PMID:Induction of erythroid differentiation of K562 human leukemic cells by herbimycin A, an inhibitor of tyrosine kinase activity. 291 Apr 52


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