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

The type II beta regulatory subunit of cAMP-dependent protein kinase (RII beta) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this issue, HL-60 human promyelocytic leukemia cells were exposed to RII beta antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII beta antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII beta protein. Exposure to RII beta sense, RI alpha and RII alpha antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII beta regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells.
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PMID:An antisense oligodeoxynucleotide targeted against the type II beta regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects. 168 49

Phenotypes of cells from 12 patients with acute myelogenous leukemia (AML) were analysed by means of a fluorescence-activated cell sorter utilizing a panel of monoclonal antibodies (MAbs). A majority of the cells from peripheral blood coexpressed the antigens against MAbs CD11, CD13, and CD33 but did not express the antigens against CD1, CD3, CD4, CD5, CD8, CD19, CD20, CD21, CD41 and 42, and glycophorin A. Three out of the 12 cases expressed CD7 antigen. However, one of them showed no reaction with Tp40 MAb, whereas the others showed reaction with Leu9 and T55. The discrepancy of reactivities between Leu9 and Tp40 MAbs prompted us to study the promyelocytic leukemia cell line HL-60, which showed similar reactions against Leu9 and Tp40 MAbs. Leu9, OKT16, and T55 MAbs reacted strongly with HL60 cells, whereas Tp40 MAb, which reacted strongly with T-cell leukemia cell line Jurkat, showed no reaction. The reactivity of Leu9, OKT16, and T55 MAbs with HL-60 cells was completely inhibited after preincubation with aggregated human immunoglobulin G (AHIG), which clearly shows the existence of nonspecific binding between these 3 MAbs and HL-60 cells via Fc gamma R. On the basis of our experiments, we conclude that HL-60 cells bind nonspecifically with Leu9, OKT16, and T55 MAbs via FcRI, and this is suggestive that de novo AML cells probably behave in the same fashion. Hence, we recommend that the utilization of murine IgG2a and IgG3 MAbs should be avoided especially in cell surface analysis of myeloid leukemic cells.
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PMID:CD7 false-positive acute myelogenous leukemia and promyelocytic leukemia cell line HL-60: characterization of CD7 epitopes by four monoclonal antibodies. 171 52

We investigated the alteration of Cu,Zn-superoxide dismutase during erythroid and myeloid differentiation in order to elucidate its physiological significance in different types of cells. We measured enzyme activity and mRNA levels of superoxide dismutase in the process of differentiation to erythroid cells or myeloid cells. When human leukemia K562 cells are incubated in the presence of 80 microM hemin, benzidine-positive cells appear on day 1 and 80% of the cells become positive on day 5. During hemin-induced erythroid differentiation, Cu,Zn-superoxide dismutase activity increases 3.5-fold of the initial value and mRNA for Cu,Zn-superoxide dismutase increases prior to the activity to the same extent. On the other hand, when human promyelocytic leukemia HL-60 cells are incubated in the presence of 1.3% dimethyl sulfoxide, nitroblue tetrazolium-positive cells reach approximately 90% on day 5. During dimethyl sulfoxide-induced myeloid differentiation, the activity of Cu,Zn-superoxide dismutase decreases below 15% of the initial value on day 5 and mRNA for Cu,Zn-superoxide dismutase decreases as well. The results indicate that the synthesis of superoxide dismutase is linked with either the erythroid or myeloid differentiation program.
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PMID:Changes in Cu,Zn-superoxide dismutase gene during induced erythroid and myeloid differentiation. 180 85

Triptolide (Tri) is a diterpenoid triepoxide isolated from Tripterygium wilfordii Hook F. The effects of Tri on the colony formation of breast cancer cell lines MCF-7 and BT-20, stomach cancer cell lines MKN-45, MKN-7, and KATO-III, and promyelocytic leukemia cell line HL-60 were reported. Using Hamburger-Salmon's double layer agar technique with certain modifications, cancer cells were cultured in 0.3% agar in a highly humidified atmosphere of 5% CO2 at 37 degrees C for 14-21 d. Colonies were counted on d 14 (occasionally d 21) with the colony analyzer system CA-7A. Of the 5 solid tumor cell lines tested, 4 showed diminished colony formation in soft agar by greater than 70% of control value in Tri 10(-8) mol.L-1 (continuous exposure). The magnitudes of the inhibitory effect of Tri on most breast and stomach cancer cell lines were similar to that on the leukemia cell line HL-60. IC50 were 0.504-1.22 micrograms.L-1. The clinically achievable peak plasma concentration (PPC) of Tri was estimated as 0.15 mg.L-1, being 72-126 times higher than the IC70 of the cancer cell lines except KATO-III. The results suggest that Tri might have a potential therapeutic effect on some types of solid tumors, e.g., breast and stomach cancers.
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PMID:Inhibitory effect of triptolide on colony formation of breast and stomach cancer cell lines. 181 94

The biochemical signaling mechanisms involved in transducing the effects of tumor necrosis factor alpha (TNF alpha) and gamma-interferon (gamma-IFN) on leukemia cell differentiation are poorly defined. Recent studies established the existence of a sphingomyelin cycle that operates in response to the action of vitamin D3 on HL-60 cells and that may transduce the effects of vitamin D3 on cell differentiation (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). The effects of TNF alpha and gamma-IFN on sphingomyelin turnover were determined, and the specificity and role of sphingomyelin hydrolysis in HL-60 human promyelocytic leukemia cells with 20% hydrolysis of sphingomyelin at 15 min, 40% hydrolysis at 30-60 min, and return to base line at 2 h. The hydrolyzed sphingomyelin (18 pmol/nmol total phospholipid) was accompanied by the concomitant generation of ceramide (11.2 pmol/nmol total phospholipid). gamma-IFN also caused reversible hydrolysis of sphingomyelin with onset at 1 h and peak effect at 2 h. This sphingomyelin cycle appeared to be specific to the monocytic pathway of HL-60 differentiation, since it was not activated by retinoic acid or dibutyryl cAMP, inducers of granulocytic differentiation, nor with phorbol myristate acetate, an inducer of macrophage-like differentiation. Addition of synthetic ceramide or bacterial sphingomyelinase induced monocytic differentiation of HL-60 cells. Cell-permeable ceramide also caused prompt down-regulation of mRNA for the c-myc protooncogene. The time course of c-myc down-regulation was consistent with the action of ceramide as the mediator of TNF alpha action. These results suggest that sphingomyelin turnover may be an important signaling mechanism transducing the actions of TNF alpha and gamma-IFN with specific function in cell differentiation.
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PMID:Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation. 184 77

Differentiation-linked expression of plasminogen activator inhibitor-2 (PAI-2) was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid, dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, granulocyte-colony stimulating factor, and interleukin-6 (IL-6)] into the culture medium of a promyelocytic leukemia cell line PL-21. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amounts of the latter in the culture medium and in the cell lysate were approximately 10 times and 2,500 times, as much, respectively, as those of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. PAI-2 antigen was demonstrated in the cell lysates of various leukemia cells by Western blotting technique using a monoclonal antibody against the PAI-2 purified from PL-21 culture medium. PAI-2 antigen was frequently detected in the plasmas from the patients whose peripheral leukocytes were more than 10,000/microliters.
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PMID:[Production and secretion of the plasminogen activator inhibitor type-2 in a leukemia cell line]. 187 Feb 66

When the leukemia cells in 14 patients with acute promyelocytic leukemia (APL) were induced by all-trans retinoic acid (RA) treatment, the activity of protein kinase C (PKC) increased with the differentiation. In the control cells, the activity of PKC was only 47 +/- 39.3 pmol.mg-1/min, while it was 149.3 +/- 150.1 pmol.mg-1/min after differentiation. There were 90.1 +/- 7.2% promyelocytes in the control group, and 8.9 +/- 5.6% in the induction group. Therefore, we think that there is a close correlation between PKC and the differentiation of promyelocytic leukemia cells.
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PMID:Protein kinase C in the promyelocytic leukemia cell differentiation of granulocytes. 187 93

Tiazofurin and retinoic acid synergistically induced differentiation and inhibited colony formation in HL-60 human promyelocytic leukemia cells in cell culture. The synergism was the result of different mechanisms of action, since the effect of tiazofurin, unlike that of retinoic acid, was prevented by addition of guanosine. Since it has been shown that tiazofurin down-regulated the expression of c-Ki-ras oncogene, and retinoic acid that of the myc oncogene, the joint impact of these drugs is of clinical interest particularly in end-stage leukemia where the therapeutic usefulness of tiazofurin has recently been demonstrated.
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PMID:Synergistic action of tiazofurin and retinoic acid on differentiation and colony formation of HL-60 leukemia cells. 196 20

Retinoic acid (RA) induces terminal granulocytic differentiation of the HL-60 promyelocytic leukemia cell line as well as certain other human myeloid leukemias. Specific RA receptors that are members of the steroid-thyroid hormone superfamily of nuclear transcription factors have recently been identified. We developed an HL-60 subclone that was relatively resistant to RA-induced differentiation. Specific nuclear RA receptors in this RA-resistant subclone had a decreased affinity for RA and exhibited a lower molecular weight compared with nuclear RA receptors from the RA-sensitive parental HL-60 cells. Retroviral vector-mediated transduction of a single copy of the RA receptor (RAR-alpha) into this RA-resistant HL-60 subclone restored the sensitivity of these cells to RA. These observations indicate that RAR-alpha plays a critical and central role in mediating RA-induced terminal differentiation of HL-60 leukemia cells.
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PMID:Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha). 2708 49

As the number of long-term survivors of childhood leukemia increases, growth retardation has emerged as a significant complication. Treatment of these children with growth hormone (GH) has been suggested and sporadically implemented. We, therefore, studied the effect of human GH (hGH) and its by-product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose-dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF-1. Similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia (ALL) of childhood and four acute myelogenous leukemia (AML) patients were studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01) in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL, respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1 may promote leukemic blast cell replication in vivo, and the supplemental administration of hGH to leukemia patients in remission must be carefully monitored for early relapse.
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PMID:Human growth hormone and insulin-like growth factor-1 enhance the proliferation of human leukemic blasts. 199 9


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