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)

This study was designed to investigate the biologic and molecular basis of the aggressive behavior of high-grade post-thymic T-cell malignancies. Freshly frozen tumor tissues from (1) human T-cell leukemia/lymphoma virus type I (HTLV-I)-positive adult T-cell lymphoma (ATL) (7 cases), (2) HTLV-I-negative aggressive T-cell lymphoma (12 cases), and (3) HTLV-I-negative nonaggressive T-cell lymphoma (11 cases) were studied for the expression of several growth-related genes or proliferation antigens including interleukin-2 receptor (IL-2R), Ki-67, transforming growth factor-beta (TGF-beta), topoisomerase, and the multidrug resistance (MDR) gene by immunohistochemistry and Northern blot hybridization. Our results showed that tumor cells associated with HTLV-I and anaplastic morphology had an enhanced expression of Ki-67, TGF-beta, and topoisomerase, as compared to nonaggressive T-cell lymphoma. The expression of IL-2R was limited to ATL and one Ki-1 lymphoma. The MDR gene was frequently expressed in ATL, but only infrequently in other, HTLV-I-negative, malignancies. Clinical progression or relapse was associated with the expression of MDR, in addition to an increased expression of Ki-67. We therefore conclude that the aggressive clinical behavior of high-grade T-cell lymphoma may result mainly from the high proliferative activity of tumor cells, but the association with HTLV-I and clinical relapse is further complicated by the development of drug resistance.
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PMID:Expression of growth-related genes and drug-resistance genes in HTLV-I-positive and HTLV-I-negative post-thymic T-cell malignancies. 167 81

Nicotinamide methyltransferase (Nmd CH3transferase) activity increased in the liver of mice after i.p. transplantation of Ehrlich ascites tumor (ascitic form), but not in the liver of mice with acute inflammation induced by the i.p. administration of D-galactosamine, and it rather showed a decrease together with necrosis after carbon tetrachloride administration. When Nmd CH3transferase activity of rat hepatocytes in primary culture was investigated with the addition of dexamethasone, epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha and N1-methylnicotinamide (1-CH3Nmd), changes in activity were not correlated with DNA synthesis, suggesting that the increase of this enzyme activity in the tumor host liver was not directly related to liver cell proliferation. Thus, in order to make use of the increase of this enzyme activity as a tumor burden marker, a procedure for its estimation by measuring the blood level of 1-CH3Nmd, a metabolite of Nmd produced by Nmd CH3transferase, was established. The 1-CH3Nmd level in the blood of mice bearing Ehrlich ascites tumor 4 h after s.c. loading of Nmd (500 mg/kg body weight) was closely correlated with this enzyme activity in the liver (r = 0.835, P less than 0.00001) from the early to the terminal stage of tumor development. Furthermore, similar correlations were seen in the animal groups bearing various other tumors, such as s.c. implanted Ehrlich ascites tumor (solid form) and i.p. implanted sarcoma S-180, hepatoma MH-134, Yoshida ascites sarcoma and leukemia L-1210, but not solid tumors such as Lewis lung carcinoma and melanoma B-16, although almost all of the animals bearing these tumors showed a higher enzyme activity than their control normal animals.
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PMID:N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden. 183 57

We have previously demonstrated (Guan X.-P., Hromchak, R. A., and Bloch, A. (1989) Cancer Commun. 1, 111-115) that ML-1 human myeloblastic leukemia cells differentiate to monocyte/macrophage-like cells by the sequential action of competence and progression factors. Tumor necrosis factor-alpha, transforming growth factor-beta, and the phorbol ester tetradecanoylphorbol acetate were found to induce competence, whereas a 77-kDa glycoprotein (DF77) isolated from mitogen-stimulated human leukocyte-conditioned medium initiated progression. In this communication we show DF77 to be an isoform of human transferrin. Hemin or soluble iron complexes did not induce differentiation progression, suggesting that the participation of transferrin in ML-1 cell differentiation may not be related to its iron-carrying capacity.
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PMID:Identification of transferrin as a progression factor for ML-1 human myeloblastic leukemia cell differentiation. 186 25

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

Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta 1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta 1 promoter. To understand further the regulation of TGF-beta 1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta 1 mRNA and protein. Moreover, TGF-beta 1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta 1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-beta in vivo.
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PMID:Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene. 192 42

Previous studies have revealed a consistent defect in the cycling behavior of primitive neoplastic progenitor cells in patients with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML). This is manifested both in vivo and in long-term cultures of CML cells as an increased rate of turnover amongst Ph1-positive progenitor cell types whose counterparts in normal individuals are mainly quiescent. To determine whether this deregulated proliferative activity of primitive Ph1-positive cells might be explained by a perturbation in the production of growth factors that regulate the turnover of primitive normal cells, the possibility of either autocrine or paracrine mechanisms of Ph1-positive cell stimulation was investigated. Northern blot analysis of total cellular RNA extracted from various CML blood cell populations showed no evidence of increased expression of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-3, IL-6, or tumor necrosis factor-alpha (TNF-alpha) compared with analogous normal peripheral blood cell populations in which transcripts for most of these growth factors are not detectable. A similar analysis of RNA extracted from the adherent layer of 4-week-old long-term cultures established from CML marrow (in which the Ph1-positive cells typically disappear) or from CML blood seeded onto normal marrow adherent layers (in which Ph1-positive cells typically persist) also revealed no difference in growth factor production compared with analogous cultures established with exclusively normal cells. For some of the growth factors studied, the assessment of bioactivity detectable in the medium confirmed the RNA data. There was also no evidence of a decreased production of putative inhibitors of primitive hematopoietic cells, i.e. transforming growth factor-beta and macrophage inflammatory protein-1 alpha by CML versus normal cells or cultures. These results do not support the existence of BCR-ABL induced autocrine or paracrine mechanisms in CML and suggest that constitutive activation of events normally dependent on growth factor receptor stimulation is more likely to underlie the lack of proliferation control exhibited by primitive Ph1-positive cells.
Leukemia 1991 Oct
PMID:Lack of evidence for abnormal autocrine or paracrine mechanisms underlying the uncontrolled proliferation of primitive chronic myeloid leukemia progenitor cells. 196 Oct 20

ML-1 human myeloblastic leukemia cells, suspended in RPMI-1640 medium, differentiated to monocyte or macrophage-like cells when either tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), or tetradecanoylphorbol acetate (TPA) was added prior to or simultaneously with fetal bovine serum (FBS). When FBS was applied first, and followed, after washing, by the cytokines or by TPA, maturation did not occur. A 77 kDa glycoprotein (DF77), isolated from human leukocyte-conditioned medium and present in FBS, was capable of replacing FBS for induction of differentiation. Thus, in this cell system, TNF-alpha, TGF-beta, and TPA acted as competence factors, whereas DF77 acted as the progression signal. Optimal competence was established after exposure of the cells to TPA or to either of the cytokines for approximately 2 or 30 min, respectively. After removal of the factors, competence was retained for approximately 3 hr before it declined. These results demonstrate that the initiation of ML-1 human myeloblastic leukemia cell differentiation relied upon the sequential and ordered input of competence and progression signals.
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PMID:Tumor necrosis factor-alpha, transforming growth factor-beta, and tetradecanoylphorbol acetate: competence factors for ML-1 human myeloblastic leukemia cell differentiation. 198 43

Acute myelofibrosis is often associated with acute megakaryoblastic leukemia (AMKBL). Although the exact mechanism for the progression of myelofibrosis in AMKBL is unclear, certain humoral factors from megakaryoblastic cells, the precursors of platelets, may be involved in the enhancement of collagen synthesis by bone marrow fibroblasts. The present study, therefore, is an investigation of the possible pathogenic role of transforming growth factor-beta (TGF-beta), known to be a very potent collagen-stimulating factor found in platelets in the myelofibrosis of AMKBL. The results obtained were as follows: (1) Conditioned media from peripheral megakaryoblasts taken from an AMKBL patient and from established megakaryoblast cell lines (MEG-01) had much greater stimulatory effects on collagen synthesis in bone marrow fibroblasts than conditioned media from other leukemic cell types. (2) Based on an assessment of soft agar colony formation, there was greater TGF-beta activity in media that had been conditioned from megakaryoblasts than in media from other leukemic cell types. (3) When compared with other leukemic-cell types, megakaryoblasts showed substantially greater expression of TGF-beta mRNA that was hybridized at 2.5 kb with a TGF-beta cDNA probe, and TGF-beta polypeptides were detected at 13 Kd with anti-TGF-beta antibodies. (4) The addition of the anti-TGF-beta antibody inhibited the stimulatory effects of the megakaryoblast conditioned medium on collagen synthesis in bone marrow fibroblasts. These results clearly suggest that megakaryoblasts produce and secrete an active form of TGF-beta and stimulate collagen synthesis in bone marrow fibroblasts in a paracrine manner.
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PMID:The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. 231 61

The effects of transforming growth factor-beta (TGF-beta) on the blast progenitors from nine acute myeloblastic leukemia patients were studied in methylcellulose and suspension cultures. Leukemic blast progenitors undergo terminal divisions with a limited differentiation in methylcellulose culture, making blast colonies. Blast progenitors can renew themselves. The self-renewal can be reflected by secondary colony formation after replating primary blast colonies in fresh methylcellulose media and by the exponential growth of clonogenic cells in suspension culture. TGF-beta suppressed primary and secondary colony-formation in methylcellulose culture. Furthermore, TGF-beta suppressed the recovery of clonogenic cells in suspension. The results indicate that TGF-beta is effective in inhibiting not only terminal divisions but also self-renewal of leukemic blast progenitors.
Leukemia 1989 Aug
PMID:Inhibition of the in vitro growth of blast progenitors from acute myeloblastic leukemia patients by transforming growth factor-beta (TGF-beta). 247 59

Tumor necrosis factor-alpha and transforming growth factor-beta, like 12-O-tetradecanoylphorbol 13-acetate, induce differentiation of ML-1 human myeloblastic leukemia cells along the monocyte path. As measured at 5 min following exposure of the cells to either of these agents, extensive translocation of protein kinase C from the cytosolic to the membrane fraction occurred. A correlation was observed to exist between protein kinase C translocation, cell differentiation, and cessation of cell growth induced by transforming growth factor-beta and tumor necrosis factor-alpha.
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PMID:Induction of protein kinase C translocation and cell differentiation in ML-1 human myeloblastic leukemic cells by tumor necrosis factor-alpha, transforming growth factor-beta, or tetradecanoylphorbol acetate. 263 23


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