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)

Radiation leukemia virus (RadLV)-induced preleukemic (PL) latency is characterized by the appearance of virus-infected PL cells in the thymus. The survival of these PL cells is dependent upon autostimulation with interleukin 4 (IL-4). We have intervened prophylactically in RadLV-induced preleukemia by using cyclosporin-A (CSA), which inhibits IL-4 production, and an immunotoxin (ITx) that kills PL cells. CSA efficiently inhibited IL-4 secretion from RadLV-induced PL and leukemic cells, and its administration to PL mice caused a significant delay in their death. An ITx consisting of anti-RadLV glycoprotein-70 (gp70) antibody coupled to ricin A chain efficiently inhibited protein synthesis in virus-infected cells in vitro and, when injected into PL mice, also delayed their death. Combined treatment with CSA and ITx prevented 75% of the treated PL mice from developing lymphoma. These results show that the development of malignancy from a premalignant state can be averted by a combination of therapeutic modalities that decrease the size and growth rate of the premalignant cell population.
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PMID:Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin. 173 46

Intrathymic inoculation of radiation-leukemia virus (RadLV) into C57BL/6 mice induces a population of pre-leukemic (PL) T cells which progress into clonal, mature thymic lymphomas after a latency period of 3 to 5 months. In order to understand how PL cells are retained in the thymus for a prolonged period of time we determined whether RadLV infected cells secrete and/or respond to a T-cell growth factor that may be involved in the long-term maintenance of a thymic PL-cell pool. We have previously found that in vitro proliferation of RadLV-infected PL cells is IL-4-dependent. Here we show that RadLV induces IL-4 secretion and IL-4 receptor (IL-4R) expression in normal thymic lymphocytes. RadLV-infected PL thymocytes express IL-4R and secrete IL-4. Their IL-4 secretion could be enhanced if incubated in the presence of RadLV and this enhancement was inhibited by anti-RadLV antibodies. Several RadLV-induced lymphoma lines secreted IL-4 and/or expressed IL-4R, but these features were not essential for their continuous growth. The results suggest that RadLV induces IL-4-dependent autocrine growth which maintains a population of PL T cells in the thymus. Transition from a PL state to overt thymic lymphoma involves emancipation of a PL cell from IL-4 dependency.
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PMID:Induction of IL-4 secretion by the radiation leukemia virus (RadLV): role in autocrine growth stimulation of RadLV infected pre-leukemic cells. 173 16

We investigated the proliferative effects of interleukins 1-7 (IL-1 to -7) on leukemic cells from 10 patients with T-lineage acute lymphoblastic leukemia (T-ALL). Five patients had CD7+4-8-acute leukemia, one had CD5+ acute leukemia, and four had CD1+ acute leukemia. To examine the proliferative effect of each interleukin, 3H-TdR incorporation method was used. In the presence of IL-1, no increase in 3H-TdR incorporation was observed for any of the T-ALL cells. With IL-2, 3H-TdR incorporation increased in cells from 5 out of 10 T-ALL patients, including those with CD7+4-8-, CD5+, and CD1+ acute leukemia. In the presence of IL-3 or IL-6, 3H-TdR incorporation increased in cells from 2 out of 5 patients with CD7+4-8- acute leukemia. However, CD5+ or CD1+ acute leukemia cells were not stimulated by IL-3 or IL-6. With IL-4, 3H-TdR incorporation was increased in the cells from 2 out of 5 patients with CD7+4-8- acute leukemia and in the cells of 2 of those with CD1+ acute leukemia. IL-5 increased the 3H-TdR incorporation by cells from 2 out of 5 patients with CD7+4-8- acute leukemia and 1 patient with CD1+ acute leukemia. IL-7 increased 3H-TdR incorporation in cells from all five CD7+4-8- acute leukemia and 2 of those with CD5+ or CD1+ leukemia. No synergistic effect was found when IL-7 and other cytokines were added to cells from the 3 patients with CD7+4-8- acute leukemia who were tested.
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PMID:Effects of interleukins 1-7 on the proliferation of T-lineage acute lymphoblastic leukemia cells. 176 57

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
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PMID:Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. 188 23

Using colony assays in semi-solid media, several investigators have shown that supernatants (SN) of normal and malignant human B-cells can stimulate the growth of granulocyte-macrophage (GM) progenitor cells. So far macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) have been identified as potential colony-stimulating activity (CSA) present in B-cell SN. However, other CSAs such as GM-CSF, G-CSF, IL-1-beta, IL-3, and IL-4 may also be candidates in this respect. Several human B-cell lines (CL) were screened for the expression of the respective genes at the mRNA and protein level. Constitutive production of GM-CSF was detected in the lymphoblastoid CL Wi-L2-729-HF2 and in the Burkitt line Raji. The signal intensity of specific transcripts and the amount of protein being secreted increased upon exposure to the phorbol ester PMA. The hybridoma line HB-564 also expressed the GM-CSF gene, but required prior stimulation with PMA. 3H-thymidine incorporation of Raji and Wi-L2-729-HF2 cells was unchanged in the presence or absence of a specific neutralizing sheep anti-GM-CSF serum, suggesting that GM-CSF did not serve as an extracellular autocrine growth factor. The expression of the GM-CSF gene was independent of the proliferative state (log phase growth versus plateau phase growth) and of the presence of serum in cultures of the respective CL. The expression of G-CSF, IL-1-beta, IL-3, and IL-4 genes was not detectable in the CL at the mRNA level.
Leukemia 1991 Aug
PMID:Screening for expression of cytokines with hematopoietic growth factor activity by permanent human B-cell lines. 188 24

We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-I-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31-32, a region found to be deleted in a number of patients with acquired 5q- abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5'-flanking region of the human IL-9 gene that may play an important role in the control of IL-9 gene expression. The 5'-regulatory region of the human IL-9 gene also contains sequences identified in the 5'-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-I-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O-tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5'-flanking region of IL-9 gene upstream from the firefly luciferase ciferase report gene indicated that the 0.9-kb Smal-Sacl fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL-9 gene in HTLV-I-transformed cells. These results will now allow us to study the regulatory mechanism of IL-9 gene expression in normal and leukemic human T cells.
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PMID:Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells. 190 Dec 33

We describe the unique characteristics of leukaemic basophils from a patient with chronic myelogenous leukaemia (CML). The leukaemic cells were immature basophil-like blasts and expressed CD4, CD7 and HLA-DR in addition to CD13 and CD33. Both immunoglobulin and T cell receptor genes were retained in germline configurations. Interleukin-1 (IL-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as IL-3 or IL-4 enhanced the proliferation and differentiation of leukaemic cells and only basophils were generated from in vitro culture. These results suggest that basophil progenitors expressing CD4, CD7 and HLA-DR may be involved in the development of basophilic crisis of CML and that both IL-1 and GM-CSF may act on basophil progenitors as well as IL-3 or IL-4.
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PMID:Characterization of leukaemic basophil progenitors from chronic myelogenous leukaemia. 204 82

A new human leukemia cell line, designated as ME-1, was established from the peripheral blood leukemia cells of a patient with acute myelomonocytic leukemia with eosinophilia (M4E0). This cell line has the characteristic chromosome abnormality of M4E0, inv(16) (p13q22). When cultured in RPMI 1640 medium containing 10% fetal calf serum, ME-1 cells were monoblastoid, but with the addition of cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, or medium conditioned by phytohemagglutinin-stimulated human peripheral leukocytes (PHA-LCM), the cells exhibited differentiation to macrophage-like cells. PHA-LCM also promoted eosinophilic-lineage differentiation of this cell line, although IL-5 did not do so. To elucidate the mechanism of proliferation and differentiation of ME-1 cells, we studied the effect of a potent inhibitor of protein kinase C, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), on colony formation of ME-1 cells. H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL-4. These results indicate that the proliferation and differentiation of ME-1 cells by IL-3 or GM-CSF were related to the activation of protein kinase C, while those by IL-4 involved other regulatory systems. ME-1 cells should be useful for studying the pathogenesis of M4E0 and the mechanisms of proliferation and differentiation of leukemic and normal progenitors by cytokines.
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PMID:Establishment and characterization of a new human leukemia cell line derived from M4E0. 207 80

We investigated the induction of tissue factor by lymphokines in human monoblastic leukemia cell lines (U937) and leukemic cells from AML (acute myelogenous leukemia) patients. After incubation for 24 h, IL-2 enhanced the intracellular tissue factor 15-fold with U937 cells, and GM-CSF enhanced it 6-fold. In contrast, other lymphokines, such as IL-1-alpha, IL-1-beta, IL-3, IL-4 and G-CSF, did not affect the activity of tissue factor. The leukemic blasts, depleted of T-lymphocytes, taken from five out of 16 AML patients showed a 2.5-14-fold increase in the activity of tissue factor per cell following incubation with 200 u/ml of IL-2 for 72 h. The IL-2 induced tissue factor activity more markedly than GM-CSF. Tissue factor stimulation by IL-2 did not correlate with the expression of the IL-2 receptor, Tac, but correlated well with FAB classification of AML cells. IL-2 responders were found in M4 and M5 subtypes only, but not all M4/M5 leukemias responded to IL-2. These findings indicate that IL-2 can mediate the tissue factor induction in the monocytic type of AML and the effect is not mediated by Tac receptors. This may shed a new light on our understanding of hypercoagulability in acute monoblastic leukemia.
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PMID:Induction of tissue factor by interleukin-2 in acute myelogenous leukemia (AML) cells. 208 39

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


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