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 describe an activation Ag Me14/D12 that appears early after T cell activation and is absent in resting T lymphocytes. Me14/D12 is a nondisulfide-linked heterodimeric structure containing two polypeptide chains of 33,000 and 38,000 Da. The expression of Me14/D12 on resting T lymphocytes can be induced by different activation stimuli such as the lectins PHA and Con A, the phorbol ester PMA, and anti-CD3 mAb. The induction of mRNA for Me14/D12 (gp33-38) in PHA-activated T lymphocytes precedes that of IL-2R gene transcripts by more than 20 h. Me14/D12 mRNA was detectable as early as 2 h after the onset of activation and mRNA for the IL-2R only after 24 h. The surface expression of Me14/D12 was detectable between 12 and 24 h after activation and was maximal between 24 and 48 h. Several T leukemia cell lines express the Me14/D12 Ag. On Me14/D12- cell lines, PMA and IFN-gamma induced surface expression of Me14/D12. Once Me14/D12 Ag were expressed on Jurkat cells after stimulation with either PMA or IFN-gamma, the binding of mAb Me14/D12 induced the production of significant amounts of IL-2 and of Ca2+ mobilization from internal stores. Comparative biochemical studies clearly demonstrate that Me14/D12 (gp33-38) is different from the CD69 molecular complex defined by mAb MLR3 and AIM.
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PMID:gp33-38, an early human T cell activation antigen. 167 42

IL-1, IL-4, and IL-6 had no effect on hairy cell (HC) proliferation in vitro. Anti-mu and low molecular weight B cell growth factor (LBCGF) and tumor necrosis factor alpha (TNF-alpha) stimulated the proliferation of a minor subpopulation of HCs detected by double immunocytochemical staining. None of these cytokines had any effect on HC differentiation as measured by immunoglobulin secretion. It is concluded that none of the above growth factors are central to HC proliferation in-vivo. Since alpha-interferon IFN-alpha, but not IFN-gamma, consistently inhibited any proliferation observed, it seems likely that this monokine has a direct antiproliferative effect in vivo.
Leukemia 1990 May
PMID:The effect of cytokines, including IL-1, IL-4, and IL-6, in hairy cell proliferation/differentiation. 220 27

The monoblastlike leukemia cell line, U-937, is induced to differentiate into monocytelike cells by incubation with 200-500 U/ml of recombinant human immune interferon (IFN-gamma) judging from capacity to reduce nitroblue tetrazolium. At least an additive differentiation-inducing effect was found between IFN-gamma and 1-100 nM retinoic acid (RA). A marked synergistic differentiation-inducing effect was found between IFN-gamma and 0.1-1.0 nM 1 alpha,25-dihydroxycholecalciferol (1,25[OH]2D3). It is also shown that U-937 can be primed for differentiation by treatment for approximately one day with 1,25(OH)2D3 followed by exposure to IFN-gamma. Priming of these cells does not depend on the normal rate of RNA synthesis, as it occurs even better in the presence of cordycepin, suggesting that a decrease in RNA synthesis favors IFN-induced differentiation. Actually, the addition of cordycepin during initial incubation with IFN increased the subsequent response to IFN-gamma (and also to RA and 1,25[OH]2D3). These results, indicating that combinations of IFN-gamma and either RA or 1,25(OH)2D3 induce differentiation of U-937, may be of importance in combination biotherapy of leukemia.
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PMID:Combinations of interferon-gamma and retinoic acid or 1 alpha, 25-dihydroxycholecalciferol induce differentiation of the human monoblast leukemia cell line U-937. 241 82

We studied the effects of gamma interferon (IFN-gamma) on HLA class I gene expression, differentiation, and proliferative capacity of K562 human leukemia cells. In the uninduced state, K562 cells show little or no class I gene expression but actively express the erythroid-specific gamma-globin gene as well as genes associated with cell proliferation, including the transferrin receptor, c-myc, and alpha-actin genes At both the surface protein and mRNA levels, IFN-gamma induces class I and beta 2-microglobulin gene expression, but does not alter the expression of the gamma-globin, transferrin receptor, c-myc, or alpha-actin genes. A 10-fold maximal induction of both class I surface protein and mRNA occurs at 48 h and is reversible upon withdrawal of IFN-gamma from the culture medium. In vitro nuclear run-on transcription assays were performed to directly establish that IFN-gamma exerts an early effect at the level of transcription, with maximal transcription rates occurring within 4 h. The difference between the time course of transcription induction and that of mRNA accumulation suggests that the regulation of class I gene expression in this human leukemic cell line also involves posttranscriptional mechanisms. Measurements of cell proliferation rates and cell cycle distribution, as well as the reversibility of the effects of IFN-gamma, demonstrate that the selective induction of class I genes in these cells occurs in the absence of differentiation.
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PMID:Gamma interferon and 5-azacytidine cause transcriptional elevation of class I major histocompatibility complex gene expression in K562 leukemia cells in the absence of differentiation. 243 Dec 85

We have investigated the direct effects of interferon (IFN) on hairy cells (HCs) isolated from patients with hairy cell leukemia using one- and two-dimensional gel electrophoresis. We have previously characterized the induction of synthesis of 10-16 specific proteins by IFN-alpha 2b in HCs, as analyzed by one-dimensional electrophoresis. By two-dimensional electrophoresis, we have now confirmed this induction and shown that the synthesis of the same number of specific proteins is down-regulated in HCs exposed to IFN-alpha 2b. When compared to HCs, fewer proteins are induced by IFN-alpha 2b in other normal, or neoplastic, lymphoid cells. We also report that protein induction occurs in HCs exposed in vivo to IFN-alpha 2b. We have demonstrated the presence of tubuloreticular structures in the cytoplasm of HCs exposed to IFN-alpha 2b in vitro, using transmission electron microscopy. We now report that these too are seen in HCs exposed to IFN in vivo during therapy. We investigated the effects of IFN-gamma on HCs and found that it also induces specific proteins. The pattern of induced proteins is distinctly different after IFN-gamma exposure in vitro. The fact that such induction occurs suggests that HCs possess also a receptor for IFN-gamma. These results demonstrate that there are direct effects of IFN-alpha on HCs and that such direct effects might be important in the antitumor activity of IFN-alpha in hairy cell leukemia.
Leukemia 1987 Apr
PMID:Action of interferons in hairy cell leukemia. 244 30

Hairy cell leukemia (HCL) is a pre-plasma B cell tumor which responds to interferon (IFN)-alpha therapy. In vitro, B cell growth factor (BCGF) can induce proliferation of hairy cells. We have investigated the effect of in vitro and in vivo treatments with different recombinant IFN on the capacity of hairy cells to proliferate in response to human BCGF. In vitro treatment of leukemic cells from HCL patients with recombinant IFN-alpha-2 (5/5 cases) or IFN-beta (4/5 cases) resulted in a marked inhibition of the BCGF-dependent response. This suppressive effect was obtained with IFN concentrations of 1000, 100 IU/ml, and even occasionally 10 IU/ml. In contrast, no such inhibition was observed with IFN-gamma, despite the presence of specific IFN-gamma receptors on hairy cells at densities similar to receptors for IFN-alpha/beta. The IFN-alpha-induced suppression of the proliferative response of hairy cells to BCGF was also observed in vivo in two patients within 6-12 hr after administration of single doses of IFN-alpha. When hairy cells were maintained in culture for 1 week, they recovered their capacity to be stimulated by BCGF. This reversion was also shown in vivo in hairy cells isolated 1 week after IFN administration. Since in vivo growth of hairy cells could possibly result from the autocrine secretion of BCGF, we propose that the therapeutic effect of IFN-alpha on HCL may be due in part to an inhibition of such autocrine loop.
Leukemia 1987 Aug
PMID:Proliferative response of hairy cells to B cell growth factor (BCGF): in vivo inhibition by interferon-alpha and in vitro effects of interferon-alpha, -beta, and -gamma. 244 36

Serum-free culture conditions would be preferable when studying the cellular and molecular regulation of B lymphocyte activation, proliferation and differentiation. We describe here the morphological and functional differentiation of chronic B-lymphocytic leukaemia (B-CLL) cells from 10 patients cultured in serum-free medium. When exposed to the phorbol ester TPA, cells from 8/10 cases expressed blastoid morphology and secreted significant levels of monoclonal IgM. The addition of 0.5% newborn calf serum to the serum-free medium increased both the spontaneous and TPA-induced IgM secretion of B-CLL cells by a factor of 6 and 7, respectively. Compared with TPA, significant but lower levels of IgM secretion and morphological differentiation were observed with native purified leucocyte interferon-alpha (IFN-alpha) (6/8 patients), some batches of recombinant IFN-alpha 2 (5/8 patients) and recombinant IFN-gamma (4/8 patients) in a dose-dependent and specific manner. Preactivation of B-CLL cells with TPA or anti-mu antibody was not necessary for the IFN-induced functional maturation. Significant DNA synthesis was not observed with any of the inducers used. These studies show that B-CLL cells can be induced to differentiate under serum-free conditions in response to physiological and non-physiological ligands.
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PMID:Induction of IgM secretion by chronic B-lymphocytic leukaemia cells in serum-free medium: effects of interferon-alpha, -gamma and phorbol ester. 245 Jul 4

Interferons (IFNs), in addition to inducing an antiviral state in uninfected cells, are able to affect cell physiology, including cell differentiation. In this respect hematopoiesis is certainly the area in which most data have accumulated. In general IFN-alpha or -beta inhibit cell growth of normal progenitors of hematopoietic lineages. In leukemia cell cultures IFNs may either stimulate or inhibit cell growth and differentiation. We report here different biological effects of murine (mu) IFN-alpha 1, -beta, and -gamma species on the erythroid differentiation of dimethyl sulfoxide (DMSO)-induced Friend leukemia cells. Treatment with mu recombinant IFN-beta enhances DMSO-induced FLC differentiation, whereas treatment with IFN-alpha 1 species as well as with natural and recombinant mu IFN-gamma preparations only inhibits it. All these observed effects are neutralized by monoclonal antibodies against IFN-alpha, -beta, and -gamma species. When mu fibroblast IFN (a mixture of alpha and beta species) was used, the inhibitory effect attributable to IFN-alpha was partly overshadowed by the simultaneous presence of a majority of IFN-beta molecules exerting the opposite effect. This is in agreement with data obtained neutralizing fibroblast IFN preparations with excess amounts of monoclonal antibodies against IFN-beta (G.B. Rossi et al., 1988, "The Status of Differentiation Therapy of Cancer," Raven Press, New York) and with our previous reports indicating that mu fibroblast IFN can either enhance or inhibit DMSO-induced differentiation when administered at low (less than 500 U/ml) or high (greater than 5000 U/ml) doses, respectively. The inhibitory effect of IFN-alpha 1 on cell differentiation is not linked to any inhibitory effect on cell growth. Results obtained analyzing the effect of IFN-alpha 1 and -beta on various IFN-resistant FLC clones indicate that different mechanisms underlie the stimulatory effect of IFN-beta and the inhibitory effect of IFN-alpha 1. These results shed light on possibly distinct physiological roles of the various species of IFNs.
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PMID:Opposite effects of murine interferons on erythroid differentiation of Friend cells. 246 Sep 93

The development of non-specific resistance to tumors following stimulation with poly(maleic-acid-styrene)-conjugated neocarzinostatin (SMANCS), a polymer-conjugated derivative of neocarzinostatin, was investigated in mice. The growth of syngeneic solid tumors (Meth-A fibrosarcoma and RL male 1 leukemia) inoculated into BALB/c mice was suppressed after one treatment with SMANCS at doses ranging from 0.14 mg/kg to 3.4 mg/kg i.v. 24 h before tumor implantation. Since previously observations concerning SMANCS have shown that it disappeared within 1.5 h after i.v. administration in mice and that it was inactivated quickly in plasma, SMANCS evidently inhibited tumor growth by mediating non-specific resistance. In addition, the non-specific resistance to tumors stimulated by SMANCS could be passively transferred to untreated mice by serum which was shown to contain interferon (IFN) from 12 h to 20 h after SMANCS administration. However, the resistance was not produced by serum prepared from mice at 8 h or 32 h after administration presumably because of the observation that the interferon activity was only demonstrated from 12 h to 28 h after SMANCS stimulation. When the serum specimens were treated with anti-IFN-gamma antiserum, the antitumor activity of the sera was abrogated. However, no significant change was detected in the antitumor activity of the specimens following treatment with anti-IFN-alpha/beta antiserum. Treatment of mice with SMANCS and anti-IFN-gamma antiserum together resulted in the elimination of the non-specific resistance to tumors. The IFN induced in the sera of mice by SMANCS was shown to be 57% IFN-gamma and 41% IFN-alpha/beta. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-gamma, and treatment of SMANCS-stimulated mice with both anti-IFN-gamma and anti-IFN-alpha/beta antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-gamma and IFN-alpha/beta production, in this case, it is only the former which mediates the non-specific resistance to tumors.
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PMID:Stimulation of non-specific resistance to tumors in the mouse using a poly(maleic-acid-styrene)-conjugated neocarzinostatin. 248 Aug 46

Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.
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PMID:Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia. 249 71


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