Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse monocytic Mm-A cell line is a highly leukemogenic variant cell line of the monocytic and non-leukemogenic Mm-1 cell line, which developed spontaneously from mouse myeloid leukemia M1 cells. Growth-inhibitory factor (GI factor) for Mm-A cells was found in conditioned medium (CM) of differentiation inducer-resistant myeloblastic M1 cells (clone R-1). The R-1 cells were cultured with or without 2% calf serum for 2 days, and the CM was fractionated with 50% ammonium sulfate and used as the GI factor preparation (termed R1CM). When Mm-A cells were cultured with 5% (v/v) R1CM for 3 days, their growth was inhibited about 80%. This inhibition of Mm-A cell growth by R1CM was irreversible. This GI factor also inhibited the growth of M1 cells that had been pretreated with inducer and had expressed some differentiation-associated properties but still retained a proliferative capacity. In contrast, it scarcely inhibited the growth of untreated M1 cells. The GI factor inhibited the growth of other mouse monomyeloblastic leukemic WEHI-3B D+ cells pretreated with a differentiation inducer, retinoic acid, and mouse monocytic leukemia J774.1 cells. However, it did not affect the growth of human monocytic (U937 and THP-1) or myeloid (KG-1, ML-1, and HL-60) cell lines. These results suggest that GI factor produced by parent myeloblastic and inducer-resistant M1 cells preferentially inhibits the growth of mouse monocytic leukemia cells in intermediate stages of differentiation from myeloblastic leukemia cells to mature macrophages.
 ...
PMID:Production by undifferentiated myeloid leukemia cells of a novel growth-inhibitory factor(s) for partially differentiated myeloid leukemic cells. 311 48

The capacity for continuous proliferation (immortalization) of ML-1 human myeloblastic leukemia cells derives from their sensitivity to growth factors and their insensitivity to differentiation factors (DF) at the limiting concentrations at which these are present in the culture medium. Upon increasing the concentration of DF, or after treatment with DNA-specific anticancer agents, the cells exit the proliferation program and differentiate to monocyte/macrophage-like cells (Y. Honma, C. Honma, and A. Bloch, Cancer Res., 46: 6311-6315, 1986). The study reported here shows that when ML-1 cells, induced to differentiate with DF contained in mitogen-stimulated human leukocyte-conditioned medium (CM) are treated with the carcinogen N-nitroso-N-methylurea, their differentiation program is interrupted and proliferation is resumed at a stably increased rate of growth (doubling time, 25.1 versus 31.3 h). This "step-up" transformation is brought about by only a narrow concentration range of carcinogen, acting at a restricted time interval following differentiation induction. The step-up transformed cells are more sensitive to growth factor signals and less sensitive to DF signals than are untreated ML-1 cells. When retreated with a higher concentration of DF and the same concentration of N-nitroso-N-methylurea, the transformed cells undergo a further decrease in doubling time to 21 h. Differentiation-uninduced ML-1 cells do not respond to treatment with N-nitroso-N-methylurea, indicating that differentiation-induced cells, at an early stage of the maturation process, may be the targets for the carcinogen-mediated transformation.
 ...
PMID:Differentiation-induced ML-1 cells as targets for transformation by a chemical carcinogen. 316 46

Human myelogenous leukaemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors (DIF) in conditioned media of mitogen-stimulated human peripheral blood leukocytes. However, human DIF has not yet been well characterized. DIF is known to be a T-cell lymphokine, as it can be obtained from the T-cell line HUT-102 and can be partially purified from medium conditioned by phytohaemagglutinin (PHA)-stimulated lymphocytes. We found that monocytes also produce factor(s) that induce differentiation of human myelogenous leukaemia cell lines to cells with macrophage-like characteristics. This factor(s) has activity different from that of colony-stimulating factor(s) or interferons. We have now purified a DIF to homogeneity from medium conditioned by PHA-stimulated leukocytes using a human myeloblastic leukemia cell line, ML-1, as target cells. The purified DIF has a relative molecular mass (Mr) of approximately 17,000, with an NH2-terminal sequence the same as that of human tumour necrosis factor (TNF). Recombinant human TNF (rHuTNF) induces differentiation of ML-1 cells and an anti-pDIF monoclonal antibody can neutralize both differentiation inducing activity and cytotoxic activity of DIF and rHuTNF. The findings indicate that one of the DIF(s) produced by leukocytes is probably TNF.
 ...
PMID:Identity of differentiation inducing factor and tumour necrosis factor. 346 66

DNA-specific agents have the capacity to induce the maturation of ML-1 human myeloblastic leukemia cells to monocyte/macrophages if adequate concentrations of fetal bovine serum or mitogen-stimulated human leukocyte-conditioned medium (CM) are present in the culture medium. Fetal bovine serum and CM contain specific differentiation-inducing factors that, in conjunction with the drugs, bring about cell maturation. To examine the mechanism by which this interactive effect occurs, ML-1 cells were exposed to actinomycin D or daunomycin in various combinations with CM, using concentrations at which neither the drug nor CM, when applied individually, induced maturation to a significant extent. Pretreatment for 3 days with drug followed by treatment for 3 days with CM caused maturation of 75% of the cells, as determined by the appearance of Fc receptors. Other markers of differentiation, including alpha-napthyl acetate esterase, acid phosphatase, and morphology, also reflected the increase in maturation. The simultaneous application of drug and CM was equally effective in inducing differentiation. Pretreatment of the cells with CM followed by treatment with drug failed to induce maturation, whereas pretreatment with CM followed by a second application of CM caused the expression of Fc receptors in 62% of the cells. In contrast, pretreatment with drug followed by a second application of drug did not induce differentiation significantly. These results indicate that the drug sensitizes the cells to respond to concentrations of CM to which they would otherwise be refractive. The drug-induced sensitization is reversible. At sensitizing drug concentrations, cell viability was preserved but, as measured by radiolabeling for 1 h, total RNA synthesis was decreased by 38% and mRNA synthesis by 87%. At these drug concentrations, the synthesis of mRNA specified by all seven oncogenes examined (myb, myc, abl, fos, N-ras, sis, erb B) was decreased by 15-60%. The administration of CM subsequent to drug caused a further decrease of some mRNA levels (c-myb, c-myc) but increased the level of others (c-fos). The drug-induced lowering of mRNA levels is considered to inhibit the synthesis of proteins specifically required for G1-S transit and maintenance of the proliferation program, amplifying, thereby, the maturation signal emitted by the differentiation factors present in serum and in CM. As a result, expression of the maturation program is initiated.
 ...
PMID:Mechanism of interaction between antineoplastic agents and natural differentiation factors in the induction of human leukemic cell maturation. 346 37

Cells of the human myeloid leukaemia cell line ML-1 were exposed to differentiation inducing doses of dimethylsulfoxide (DMSO) and retinoic acid (RA). DMSO (but not RA) caused an inhibition of cell growth which was reversible. Some granulocytic maturation associated changes were induced by both agents: nuclear segmentation in 10-20% of cells, B43.4 antigen positivity. In contrast, several other markers were not induced: nucleoli persisted in almost 100% cells including the segmented ones, the nuclear membrane regions did not stain with Victoria blue B (which stains these regions in normal neutrophils), the expression of other antigens of mature neutrophils was also not induced. Maturation asynchrony and non-physiological segmentation of round and oval nuclei were observed. Examination of nucleoli on a single cell level revealed a reversible decrease of pre-rRNA synthesis in 28-48% of the induced cells. These results indicate that terminal differentiation did not occur and confirm the dissociation in induction of various differentiation markers.
 ...
PMID:Features of immaturity in cells derived from granulocytic differentiation inducer treated human myeloid leukaemia (ML-1) cells. 347 63

The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma.
 ...
PMID:Synergistic inhibitory effects of dipyridamole and vincristine on the growth of human leukaemia and lymphoma cell lines. 347 94

EO-1, an IgGl murine monoclonal antibody raised against human eosinophilic leukemia cells, reacts with eosinophils, basophils, platelets, and a few (2%) mononuclear cells but not with neutrophils. In the bone marrow, mature and immature eosinophils and basophils express the EO-1 antigen, whereas immature myeloid cells do not. The distribution of EO-1 antigen on leukemic cells is concordant with this finding, ie, typical myeloid lines (HL-60, KG-1, and ML-1) and fresh acute myelogenous leukemia cells are all unreactive with EO-1. Immunoprecipitation of an extract from surface-131I-labeled platelets with EO-1 and sodium dodecyl sulfate polyacrylamide gel electrophoresis, under reducing or nonreducing conditions, yielded a specific band of molecular weight 23,000. Previously described monoclonal antibodies reacting with eosinophils also recognize neutrophils. EO-1 is a unique antibody with specificity restricted to eosinophils, basophils, and platelets and might therefore be a valuable reagent for the study of their function and differentiation.
 ...
PMID:A monoclonal antibody reactive with human eosinophils. 348 29

Antiserum to a synthetic peptide that defines a hydrophilic region within the putative c-myb translation product was prepared in the rabbit. In lysates from exponentially growing ML-1, human myeloblastic leukemia cells, the antiserum ("anti-myb") reacted with five proteins of Mr 58,000, 75,000, 85,000, 90,000 and 105,000. Of these, only p75 and a trace of p85 were detected, by immunoblotting, in extracts derived from ML-1 cell nuclei. The proteins p58, p75 and p90 were present in readily detectable amounts only in the relatively immature myeloid cell lines ML-1 and HL-60, whereas in the more mature myeloid cell line THP-1 and in the lymphoid line BALL-1 only traces of these proteins were found. p85 and p105 were detected in lysates from all cell lines tested, including myeloid and lymphoid leukemia cells and mouse 3T3 cells. In lysates from ML-1 cells induced to differentiate to monocyte/macrophages or to granulocytes, the concentrations of p58 and p75 decreased in parallel with the cell population moving to maturity; in completely mature populations these two proteins were no longer detectable. In ML-1 cells arrested in G1 by serum depletion, the amount of p58 and p75 and to a smaller extent that of p90 was decreased, whereas the concentration of p85 and p105 remained unchanged. In nuclei from exponentially growing ML-1 cells, the antiserum or its derived immunoglobulin fraction ("anti-myb IgG") inhibited mRNA transcriptional activity by 30%. DNA synthesis was not affected. In contrast, in nuclei from differentiated ML-1 cells, the mRNA transcriptional activity was not significantly inhibited by anti-myb IgG. Similarly, in nuclei from ML-1 cells arrested largely in G1 by serum depletion for 2 days, mRNA transcriptional activity was inhibited by only 11%. Upon supplementation with serum, the mRNA transcriptional activity inhibitable by anti-myb IgG increased in parallel with the increasing rate of cell growth. The difference in total mRNA transcriptional activity observed in nuclei from cells of different growth rate was accounted for by the difference in transcriptional activity inhibitable by anti-myb IgG.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Inhibition of messenger RNA transcriptional activity in ML-1 human myeloblastic leukemia cell nuclei by antiserum to a c-myb-specific peptide. 354 99

Cell line ML-1 was established from a myelogenous leukemia of an RFM mouse. The ML-1 cells and in vitro normal mouse bone marrow cells were analyzed to determine if there was a differential sensitivity to X-ray-induced chromosome aberrations in G1 cells and/or differences in postirradiation cell cycle progression. Cells identified as being in G1 at the time of irradiation by their staining pattern after replication in 5-bromodeoxyuridine were analyzed for all types of chromosomal aberrations following X-ray doses of 0.5, 1.0, 1.5, and 2.0 Gy. ML-1 cells showed a greater sensitivity to the induction of both chromosome-type aberrations (dicentrics and terminal deletions) and chromatid-type aberrations (exchanges and deletions) compared to normal mouse bone marrow cells, which only contained chromosome-type aberrations. The presence of chromatid-type aberrations in the ML-1 cells and not normal bone marrow cells suggested a differential progression through the cell cycle for the two cell types after irradiation. Mitotic index and flow cytometric analyses were performed and showed that both cell types have a delay in progression from G2 into mitosis, but only the normal mouse bone marrow cells have a delay in progression from G1 into S, as well as delayed progression through the S phase following X-irradiation. These results indicate that the ML-1 leukemia cells have an increased radiosensitivity. This may be due to a defect in their ability to respond to DNA damage as evidenced by their lack of a G1- and S-phase delay which allows normal cells an increased time to repair DNA damage before replication. These same characteristics have been observed in ataxia telangiectasia cells and may well represent a general feature of cells with increased radiosensitivity.
 ...
PMID:Differential sensitivity of a mouse myeloid leukemia cell line and normal mouse bone marrow cells to X-ray-induced chromosome aberrations. 386 3

The growth inhibitory activity of human recombinant leucocyte A interferon (Ro22-8181: alpha-interferon) against 23 human cultured cell lines derived from leukemias and lymphomas was measured quantitatively by regrowth assay. Daudi cells were the most sensitive to it. Two T-cell lines (RPMI-8402, HUT78), three B-cell lines (Raji, Ly16, A3/Kawakami), one non-T, non-B acute lymphoblastic leukemia (ALL) cell line (KOPN-1) and three myelomonocytoid cell lines (U937, THP-1, ML-1) were moderately or slightly sensitive. Although the levels of sensitivity of these cell lines were different, cells could be killed by the recombinant alpha-interferon. Morphological changes in the sensitive cells treated with it were decreases in mitosis, pyknosis and fragmentation of the cells. Thirteen other cultured cell lines were not sensitive. The results indicated that the growth inhibitory activity of recombinant alpha-interferon is not always cell lineage-specific. There were only three cell lines whose sensitivity, expressed by the concentration required for 90% growth inhibition, was less than the several hundred units per milliliter that has usually been obtained as blood levels in clinical trials. These three included one of 10 T-cell lines and two of seven B-cell lines; none of six non-T, non-B ALL and myelomonocytoid cell lines were that sensitive. Among virus-associated cell lines, only Epstein-Barr virus-associated B-cell lines were sensitive to the interferon; adult T-cell leukemia virus-associated T-cell lines were not sensitive. It was demonstrated that recombinant alpha-interferon has a time-dependent, but not a concentration-dependent cytocidal action, indicating that optimal therapeutic schedules of recombinant alpha-interferon for cancer may be daily long-term treatment, not single or short-term large-dose therapy.
 ...
PMID:Time-dependent cytotoxic action of human recombinant alpha-interferon (Ro22-8181) in vitro and the sensitivity of various cultured leukemia and lymphoma cell lines to it. 398 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>