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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between the expression of the c-fos proto-oncogene and the expression of the class I major histocompatibility (MHC) antigens during the early stages of induced differentiation in three different leukemic cell lines was examined. In the U937 histiocytic lymphoma line TPA induced an increase in mRNA and cell surface MHC expression which followed induction of c-fos. In contrast, in the murine erythro-leukemia cell line, DMSO induced declining constitutive c-fos levels that were accompanied by declining mRNA and cell surface MHC expression. In the pluripotent HL60 promyelocytic line induction of macrophage differentiation with TPA led to c-fos induction and rising MHC levels, whereas induction of granulocyte differentiation with DMSO did not induce c-fos expression and was followed by declining MHC levels. Taken together, the results suggest that the c-fos proto-oncogene might be involved in the control of class I MHC antigen expression during differentiation.
Leukemia 1987 Mar
PMID:Expression of major histocompatibility class I genes in differentiating leukemic cells is temporally related to activation of c-fos proto-oncogene. 331 38

Leukemia is characterized by a proliferation of cells that exhibit an arrest in the normal differentiation sequence. The HL-60 promyelocytic leukemia is a useful model of the phenomenon of maturation arrest, particularly as modulated by inducers that partially restore myeloid differentiation. In this investigation, we report the development of two sublines of HL-60 and the acquisition of two others that are clonal variants of the parent cell line. Each of the sublines demonstrates an altered pattern of differentiation and resistance to one or more of the drugs that serves as an inducer of the parent line. The two cell lines developed in this study, HL-60S and HL-60I, are resistant to arabinosylcytocine (ARA-c); HL-60I is also resistant to PMA. A study of the phenotype as expressed by the granule-associated cytoplasmic enzymes revealed that each subline had a slightly different pattern of maturation in response to dimethylsulfoxide (DMSO) or ARA-c as inducers. The proliferative rate of all sublines was similar. These data demonstrate that the maturation arrest observed in this model is in part reversible. The maturation arrest observed in myeloid leukemias is due to a reversible block secondary to altered proliferative activity.
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PMID:Leukemic cell maturation: variability of the myeloid leukemic cell phenotype. 346 56

Using two-dimensional gel electrophoresis we have analyzed the pattern of phosphorylated proteins in HL-60 leukemia cells and changes associated with their differentiation into granulocyte and monocyte-like cells. In undifferentiated cells 18 spots with MW ranging from 110 to 17, kDa were individualized with high resolution and reproducibility. Myelocytic differentiation induced by dimethyl sulfoxide (DMSO) and retinoic acid (RA) resulted in a decrease of the overall phosphorylation, the disappearance of two proteins of 42 and 17 kDa, and the appearance of one new acidic protein of 46-48 kDa. These changes seem to be specifically related to this differentiation pathway since they are not found in two HL-60 subclones resistant to DMSO or RA-induced differentiation. Monocytic differentiation induced by 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] and the combination of RA + 1-B-D-arabinofuranosyl cytosine (Ara-C) was associated with the appearance of 2 proteins of 68 kDa and 2 proteins of 80 kDa located in the acidic region of the gel. The protein of 17 kDa, when disappeared completely in granulocytic-like cells was present in monocytic cells, this suggesting that its phosphorylation state may be involved in the control of the differentiation pathway of HL-60 cells. Data concerning the effect of phorbol myristate acetate (PMA) and histamine on the level of phosphorylation of various proteins in HL-60 cells have also been obtained and discussed. Our results show that the myelocytic and monocytic phenotypes are characterized by a specific pattern of phosphoproteins involving both phosphorylation and dephosphorylation reactions.
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PMID:Changes in the patterns of protein phosphorylation associated with granulocytic and monocytic-induced differentiation of HL-60 cells. 346 46

The DNase I sensitivity of total chromatin was studied in fixed cells and nuclei isolated from proliferating and terminally differentiated cells, by measuring the incorporation of labelled nucleotides into DNase-sensitive sites, and electrophoresis of DNA isolated from DNase-treated nuclei. The unfixed nuclei were sensitive to digestion at around 10 micrograms/ml, the fixed cells at 30 ng/ml DNase I concentration. Proliferating Rauscher leukemia cells were more digestible than normal spleen cells. The DNase I sensitivity of the human HL60 leukemia line decreased upon DMSO-induced differentiation but still exceeded the digestibility of nuclei from normal human peripheral blood. A novel flow-cytometric technique was developed to study DNase sensitivity at the cell level. It confirmed the relative resistance of differentiated cells to DNase I and ruled out the possibility that this could be due to an altered distribution of cell cycle phases. The overall DNase I sensitivity of chromatin was compared with the sensitivity of the c-myc gene and the myc-associated hypersensitive sites. The latter sites were detected at 1 microgram/ml DNase I in HL60 nuclei. They disappeared partially upon DMSO-induced differentiation. At 10 micrograms/ml, myc was degraded in both growing and differentiating HL60, but not in HPB cells. These data suggest that a progressive condensation of the chromatin occurs during terminal differentiation which gradually involves specific genes that need to be inactivated.
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PMID:Overall changes in chromatin sensitivity to DNase I during differentiation. 346 2

The bipotential human promyelocytic leukaemia cell line HL-60 can be induced to differentiate into monocytic or granulocytic cells by treatment with 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) or dimethylsulphoxide (DMSO) respectively. Conditioned media (CM) from 1,25(OH)2D3- or DMSO-treated cells were able to induce monocytic differentiation in fresh HL-60 cells as measured by induction of non-specific esterase and macrophage surface markers. CM from 1,25(OH)2D3-treated cells also led to a dose dependent loss of proliferative capacity in soft agar colony assays. These effects were not due to a toxic effect of the CM or to residual inducer present in the CM. gamma-interferon and GM-CSF were apparently not responsible for these effects. CM from the human histiocytic lymphoma cell line U937 led to only a low level of induction of macrophage differentiation in fresh HL-60 cells. The defect in HL-60 leukaemic cells may therefore be at the level of induction of an autonomously-produced differentiation factor.
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PMID:Differentiated HL-60 promyelocytic leukaemia cells produce a factor inducing differentiation. 347 May 75

We have previously demonstrated that a combination of interferon beta and a differentiation agent, dimethyl sulfoxide (DMSO), is cytotoxic for HL-60 cells, a human promyelocytic leukemic cell line. We now report that a combination of recombinant interferon alpha (Intron; Schering) and retinoic acid is synergistically cytostatic for HL-60 cells. Retinoic acid (RA) induced the differentiation of HL-60 cells into granulocytes. Interferon (IFN) alone at 1-1000 IU/ml had no effect on either differentiation or proliferation of HL-60 cells. The addition of 1000 IU/ml of IFN and 10(-7) M RA at the initiation of culture reduced the number of viable cells to 28% of that observed for cells treated with RA alone. The decreased number of cells was a result of decreased cellular proliferation, rather than of a cytotoxic effect of the combination. IFN-RA-treated cells differentiated more rapidly than cells treated with RA alone. In addition, the final percentage of mature cells was increased at day 7 in IFN-RA-treated cultures, as compared with RA-treated cells. Simultaneous treatment of the cells with IFN and RA decreased the concentration of RA needed to induce differentiation or to exert a cytostatic effect. Significant changes in the nuclear structure of RA-treated HL-60 cells after 24 h have been reported. Cells were pulsed with RA for 24 h, washed, and IFN added. At day 7, cell growth was inhibited to the same extent as that of cells continuously exposed to IFN-RA. However, while 70% of the continuously exposed cell differentiated, cells pulsed with RA and subsequently treated with IFN did not differentiate. The results of this investigation further support our findings that combinations of IFN and inducers of differentiation may be of importance in the treatment of leukemia.
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PMID:Recombinant human interferon alpha enhancement of retinoic-acid-induced differentiation of HL-60 cells. 347 21

Recently, a novel approach has been used in the treatment of leukemia: induction of the leukemic cells to undergo terminal differentiation. Based on its in vitro ability to induce differentiation in several myeloid leukemic cell lines, retinoic acid (RA) has been applied clinically in cases of myelodysplastic syndromes and acute myeloid and promyelocytic leukemia. In the present study we have determined in detail the ability of RA to induce expression of granulocytic functions in a human promyelocytic leukemia cell line (HL-60) and compared it with that of dimethylsulfoxide (DMSO). Several granulocytic characteristics (phagocytosis, surface adherence and generation of free radicals in response to phorbol-ester) were induced to the same degree by both agents. Other normal neutrophil functions, including lysozyme accumulation, spontaneous migration, chemotactic activity toward zymosan-activated serum (containing C5a), the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and spontaneous motility in semi-solid medium were induced by DMSO, but they were absent or incompletely expressed in RA-induced cells. In contrast, only RA induced migration toward leukotriene B4 (LTB4). Simultaneous treatment with RA and DMSO proved synergistic with respect to morphological maturation and several functions (e.g. NBT reduction), but complementary stimulation of other activities (e.g. chemotaxis, lysozyme content) could not be demonstrated. Furthermore, characteristics induced by DMSO (i.e., expression of C5a and FMLP receptors and accumulation of lysozyme) were inhibited by the addition of RA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of granulocytic functions by leukemic promyelocytic HL-60 cells: differential induction by dimethylsulfoxide and retinoic acid. 347 6

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.
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PMID:Features of immaturity in cells derived from granulocytic differentiation inducer treated human myeloid leukaemia (ML-1) cells. 347 63

Untreated, late passage HL60 promyelocytic and KG1 myeloblastic leukaemia cells did not increase proliferation with placenta or Mo T cell conditioned medium containing colony-stimulating factor (CSF) nor with partially purified, recombinant granulocyte/macrophage (GM)-CSF. However, after induction with DMSO or 1,25-dihydroxy-vitamin D3, HL60 cells showed dose-dependent increases in proliferation with crude and purified CSFs. CSF responses and macrophage differentiation were induced in KG1 cells by treatment with tetradecanoylphorbol-acetate (TPA). When cells were exposed to inducing agents for varying periods, washed and exposed to CSF, proliferative responses were related to time of exposure. Cells exposed for 1-4 d showed post-induction CSF-induced proliferation, but cells induced for 5-6 d were inhibited by CSF. Induction of CSF response appeared linked to differentiation, since KG1 cells differentiated with TPA and developed CSF-induced proliferative responses, but showed no differentiation or CSF induced proliferation after treatment with vitamin D3. When HL60 cells were continuously exposed to DMSO or vitamin D3, overall cell production was increased by placenta conditioned medium, but cultures still became senescent and died after several weeks. Cells continuously cultured with DMSO were predominantly macrophages, indicating lineages of DMSO-induced differentiation were modified by continuous culture or the presence of CSF. After treatment with chemical inducers, proliferation of myeloid leukaemia lines is stimulated by CSF, providing a model for post-deterministic regulation of normal and malignant myeloid cell production.
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PMID:Induction of colony-stimulating factor response in myeloid leukaemia cell lines. 349 21

Four human B cell lines with a mature phenotype (immunoglobulin secretion and expression of membrane markers associated with maturation) were cultured in the presence of phorbol ester (PMA), dimethyl sulphoxide (DMSO) and two conditioned media. PMA and DMSO led to changes in phenotype which suggested the cells were being activated, whilst the conditioned media resulted in increased immunoglobulin secretion, accompanied by phenotypic changes more consistent with maturation towards the plasma cell stage. The four cell lines, which had different origins (EBV-transformed normal B cell, Burkitt's lymphoma, prolymphocytic leukaemia and multiple myeloma) responded differently to the culture stimuli. These differences suggest that the changes associated with transformation affect the way in which these cells respond to agents which stimulate activation and maturation.
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PMID:Responses of 'mature' human B lymphocyte lines to inducers of maturation and activation. 349


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