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)

We found that recombinant and natural lymphotoxin differ from TNF in that they only marginally induce differentiation of human myeloblastic leukemia ML-1 cells. Even at 1,000-fold concentrations, lymphotoxin was significantly less potent than TNF. Lymphotoxin competitively, but not completely, inhibited TNF-induced differentiation. Based on studies of the two types of TNF receptors (55 kDa and 75 kDa) using monoclonal antibodies, the binding activity of lymphotoxin to the receptors was less than 1/3 that of TNF, but lymphotoxin could bind to both TNF receptors. Both receptors were involved in induction of differentiation by TNF. However, lymphotoxin, differed from TNF; it seemed to be weak in sending signals for differentiation through the 75 kDa receptor.
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PMID:Lymphotoxin and TNF differ greatly in capacity to induce differentiation of human myeloblastic leukemia ML-1 cells. 806 28

In the absence of serum, growth of ML-1 human myeloblastic leukemia cells is induced by the insulin-like growth factor-1 (IGF1) together with transferrin (Tf), whereas monocytic differentiation is initiated by the transforming growth factor-beta (TGF-beta) in combination with Tf. Initiation of growth was followed by the rapid release of arachidonic acid (AA), hydroxyeicosatetraenoic acids (HETEs) and phospholipids into the culture medium. In contrast, induction of differentiation occurred without the release of these lipids beyond the level present in control. Inhibitors of enzymes involved in the formation of AA and of HETEs, including phospholipase A2 and lipoxygenases, caused interference with growth but not with differentiation, and an inhibitor of the cyclooxygenase path affected neither growth nor differentiation. These results indicate that the initiation of ML-1 cell growth but not of cell differentiation is dependent upon the increased formation of AA and its derivatives formed primarily via the lipoxygenase path.
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PMID:Differential effect of growth- and differentiation-inducing factors on the release of eicosanoids and phospholipids from ML-1 human myeloblastic leukemia cells. 811 43

We looked for chemotaxin/interleukin 8 (CT/IL-8) activity in the culture fluids of 97 human leukemia cell lines and found it in two of the T cell lines, six of the myeloid cell lines, and one of the normal B-cell lines. It was particularly strong in the culture fluids of two cell lines. These cell lines secreted a chemotactic protein into the culture fluids under certain conditions of stimulation with phorbol-12-myristate 13-acetate (PMA), lipopolysaccharide, or hemagglutinin-P. A myeloid leukemia cell line, ML-1, secreted an inducible chemotaxin when stimulated with PMA (1 ng/ml) for 24 h. We purified the chemotaxin from ML-1 cell culture fluid using an improved procedure: concentration with DEAE-Sepharose CL-6B and CM-Sepharose CL-6B, CM-Sepharose column chromatography, and reverse-phase 5TMS-300 column on HPLC with the retention time coinciding with that of LUCT/IL-8 [Suzuki et al., 1989, J. Exp. Med. 169, 1895]. The yield was 200 micrograms protein from 6 liters of the culture fluid. The N terminus of CT/IL-8 was AVLPR-SAKELRXQXIKTYSK- - -, the same as that of LUCT/IL-8, which is constitutively secreted from lung giant cell carcinoma LU65C cells. The optimal concentration in the chemotactic activity of CT/IL-8, equivalent to that of bacterial chemotactic peptide fMet-Leu-Phe (10 nM), was found to be 5 nM. The results show that this chemotaxin is identical to LUCT/IL-8.
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PMID:Isolation and amino acid sequence of a chemotactic protein, LECT/interleukin 8, from a human myeloid leukemia cell line, ML-1. 834 17

When added to RPMI-1640 medium containing fetal bovine serum, DNA-directed antineoplastic agents such as cytosine arabinoside (araC), daunorubicin, and actinomycin D induce the monocytic differentiation of ML-1 human myeloblastic leukemia cell populations to an extent that depends upon both drug and serum concentration. Differentiation is not induced in the absence of serum or when antibodies to tumor necrosis factor-alpha and transforming growth factor-beta are added to the cultures, indicating that these serum-contained cytokines participate in initiating the differentiation process. The drug- and cytokine-dependent cell maturation, which results in the inhibition of leukemic cell growth, is achieved at much lower concentrations of drug than is required for growth-inhibition through drug-mediated cell kill. RNA- and protein-targeted agents cannot replace DNA-specific agents in the process of differentiation-induction. The DNA-specific agents render the leukemic cells responsive to the low concentrations of differentiation-inducing cytokines that are present in serum, causing them to mature, and subsequently, to cease growth. This sensitization may be a component of the clinically selective action of DNA-specific antitumor agents.
Leukemia 1993 Aug
PMID:Dynamics of interaction between DNA-specific antitumor agents and serum-contained cytokines in the initiation of ML-1 human myeloblastic leukemia cell differentiation. 835 Jun 21

The individual roles of two types of TNF receptors (55 kDa and 75 kDa) in induction of differentiation of human myeloblastic leukemia ML-1 cells were investigated using three monoclonal antibodies. The antibody htr-9, which recognizes the 55 kDa receptor, induced differentiation of ML-1 cells. Utr-1, which recognizes the 75 kDa receptor, blocked 125I-TNF binding by about 80% and inhibited by about 80% the TNF-induced NBT reducing activity. Htr-5 recognizes the 55 kDa receptor, blocked 125I-TNF binding by about 20% and inhibited by about 60% the TNF-induced NBT reducing activity. The data suggest that either of the two TNF receptors alone can mediate signals for the differentiation of ML-1 cells, and that simultaneous stimulation of both receptors will induce differentiation more effectively.
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PMID:Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells. 839 78

The c-myc gene is thought to play a role in cell proliferation and differentiation; for example, constitutive expression of an exogenously introduced c-myc gene can inhibit differentiation in hematopoietic cell lines. Expression of the endogenous c-myc gene has now been monitored during the differentiation, and associated loss of proliferation, of ML-1 human myeloblastic leukemia cells: c-myc mRNA remains detectable, at decreased levels, during differentiation along the monocyte/macrophage pathway induced with 12-O-tetradecanoylphorbol-13-acetate. c-myc protein also remains present, at undiminished levels, in mature, nonproliferative cells (assessed by immunoblotting and flow cytometry). The protein is, however, readily detectable in the cytoplasm of 12-O-tetradecanoylphorbol-13-acetate-induced cells, and some of this cytoplasmic c-myc exhibits a shift in electrophoretic mobility compared to the predominantly nuclear c-myc in uninduced cells. Furthermore, although c-myc protein continues to be synthesized in the mature cells (assessed by metabolic labeling/immunoprecipitation), loss of the protein from the cytoplasm and accumulation in the nucleus are slowed (assessed by pulse-chase metabolic labeling). These findings suggest that, during the 12-O-tetradecanoylphorbol-13-acetate-induced differentiation and loss of proliferation of ML-1 cells, c-myc protein is regulated through alterations that affect its cytoplasmic/nuclear distribution rather than its total cellular content.
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PMID:Altered cytoplasmic/nuclear distribution of the c-myc protein in differentiating ML-1 human myeloid leukemia cells. 851 29

Certain osteoclastic markers (multinucleation and tartrate-resistant acid phosphatase) were induced in human leukemia HL-60 cells by treatment with 10(-7) M 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] for 10 days. However, no formation of pits on a bone substrate by vitamin-treated HL-60 cells was detected. Expression of calcitonin receptors (CTR), another osteoclastic marker, was examined by means of the reverse transcriptase polymerase chain reaction. The human CTR-cDNA (T47D isotype) was amplified from untreated HL-60 cells, but not from cells treated with 1,25(OH)2D3. The CTR mRNA disappeared within 24 h after the treatment. Thus, 1,25(OH)2D3-differentiated HL-60 cells failed to show two intrinsic characteristics of osteoclasts, pit formation on a bone substrate and expression of CTR. We then examined the expression of CTR on established human leukemia cell lines. The CTR mRNA was expressed in myeloblastic ML-1 and promyelocytic HL-60 leukemia cells but not in more mature macrophage-like cell lines, U-937 and THP-1 cells. Neither B cell leukemia BALL-1, T cell leukemia Jurkat, promegakaryoblastic leukemia Meg-J, nor cervix uteri carcinoma HeLa S3 cells amplified the CTR products. The cDNA of BIN67-isotype CTR, that has an additional 16-amino acid insert in the putative first intracellular loop of T47D-type CTR [Kuestner et al. (1994) Mol. Pharmacol. 46, 246-255], was amplified by neither strain tested. It was suggested that the T47D-type CTR is a novel differentiation antigen of immature myeloid lineage cells.
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PMID:Expression of calcitonin receptors on human myeloid leukemia cells. 854 84

We have examined the effects of tumor necrosis factor alpha (TNF) and lymphotoxin (LT) on gelatinase (72 kDa and 92 kDa) and tissue inhibitor of metalloprotease 1 (TIMP1) secretion by human myeloblastic leukemia cells (ML-1) in vitro. TNF (0.1-30 ng/ml) significantly stimulated 92 kDa gelatinase secretion in a dose-dependent manner, but did not significantly stimulate 72 kDa gelatinase secretion. LT also significantly stimulated 92 kDa gelatinase secretion, but the stimulation was less effective compared to TNF. TNF, but not LT, concentrations at 30 ng/ml slightly stimulated TIMP1 secretion. Because 92 kDa gelatinase is thought to play a pivotal role in tumor invasion, we examined the effect of TNF or LT on ML-1 cell invasion through a reconstituted basement membrane (Matrigel). Exposure of ML-1 cells to TNF (3, 10, and 30 ng/ml) or LT (3, 10, and 30 ng/ml) stimulated ML-1 cell invasion through Matrigel in a dose-dependent manner in vitro. The data suggest that TNF- and LT-stimulated 92 kDa gelatinase secretion could play an important role in TNF- or LT-stimulated ML-1 cell invasion.
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PMID:Tumor necrosis factor alpha and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (Matrigel) with concomitant induction of 92 kDa gelatinase secretion. 855 14

mcl-1 was identified as an "early-induction" gene that increases in expression during the differentiation of ML-1 human myeloblastic leukemia cells. The mcl-1 gene product proved to be a member of the bcl-2 gene family and, like bcl-2, to have the capacity to promote cell viability. The pattern of expression of mcl-1 has now been characterized, the aim being to determine whether increased expression is consistently associated with differentiation-induction and whether expression is also associated with other changes in proliferative state or cell viability. Expression of the mcl-1 mRNA was found to increase rapidly in ML-1 cells exposed to inducers of monocyte/macrophage differentiation (phorbol esters or lymphocyte conditioned medium), but not cells exposed to an inducer of granulocyte differentiation (retinoic acid). Expression also increased rapidly in response to certain cytotoxic agents (colchicine and vinblastine), but did not increase during serum stimulation or growth-arrest in reduced serum. Increased expression of mcl-1 occurred during the initiation of cell differentiation or death and was not inhibited by cycloheximide, in agreement with the designation of mcl-1 as an early-induction gene. Increased transcription contributed to the increase in expression, and turnover of the mcl-1 mRNA was rapid. These findings suggest that mcl-1 may serve as a modulator of cell viability that can undergo rapid upregulation as well as downregulation, with upregulation harbingering the initiation of cell differentiation or death.
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PMID:MCL-1, a member of the BLC-2 family, is induced rapidly in response to signals for cell differentiation or death, but not to signals for cell proliferation. 860 Jan 56

Tretinoin tocoferil is an alpha-tocopherol ester of all-trans retinoic acid (RA) and safely used in the treatment of skin ulcer. Tretinoin tocoferil inhibited proliferation of human promyelocytic leukemia HL-60 cells and induced granulocytic differentiation of the cells, but less than RA. alpha-Tocopherol did not affect differentiation of HL-60 cells, but at high concentrations enhanced its nitroblue tetrazolium (NBT)-reducing activity and expression of surface antigen CD11b, which are markers of myelomonocytic differentiation induced by RA. Tretinoin tocoferil increased NBT reduction in HL-60 cells treated with RA. It also enhanced the differentiation of HL-60 cells induced by dimethyl sulfoxide, phorbol-12-myristate 13-acetate or 1alpha,25-dihydroxyvitamin D3 (VD3). In combination with a low concentration of VD3, it induced the NBT-reducing activity of human monoblastic U937 cells very effectively. Moreover, it enhanced the differentiation of human myelomonocytic ML-1, THP-1, P39/TSU, and P31/FUJ cells induced by VD3. In combination with VD3, it synergistically inhibited the proliferation of HL-60, U937, ML-1, THP-1, P39/TSU, and P31/FUJ cells and decreased the effective concentration of VD3 to a 10(-10) mol/L level. Because tretinoin tocoferil was reported to induce neither retinoid-related toxicity nor teratogenicity, the therapeutic advantage of the use of it in treatment of myelomonocytic leukemia is suggested.
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PMID:Enhancement of activity of 1alpha, 25-dihydroxyvitamin D3 for growth inhibition and differentiation induction of human myelomonocytic leukemia cells by tretinoin tocoferil, an alpha-tocopherol ester of all-trans retinoic acid. 860 56


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