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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin 6 (IL-6), which is suggested to play an important role in thrombocytosis, elevation of C-reactive protein, and hypercalcemia in ATL. In this study, we investigated the effects of T-cell growth factors such as interleukin 2 (IL-2) and interleukin 4 (IL-4) on IL-6 production by ATL cells in vitro. Although IL-2 and/or IL-4 enhanced the cell proliferation of freshly isolated ATL cells from seven of nine patients, IL-2 did not affect the IL-6 release in most cases. In contrast, another T-cell tropic factor, IL-4 markedly inhibited the release of IL-6 in the conditioned medium in all cases. This IL-4-mediated inhibition of IL-6 release was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Time course experiments demonstrated that IL-4 reduced the secretion of IL-6 for a prolonged period of time (more than 72 h). By Northern analysis, IL-4 reduced the transcription level of IL-6 mRNA. Furthermore, by flow cytofluorometry with the use of anti-human IL-4 receptor monoclonal antibody, ATL cells showed the significant level of IL-4 receptor on their cell surfaces without any stimulation. These data suggest that IL-4 may play an important regulatory role in the production of IL-6 in ATL.
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PMID:Inhibitory effect of interleukin 4 on production of interleukin 6 by adult T-cell leukemia cells. 840 41

Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of interleukin-1alpha (IL-1alpha). To analyze the mechanisms that lead to the expression of IL-1alpha in HTLV-I-infected cell lines, we studied regulatory regions of the human IL-1alpha promoter involved in activation of the IL-1alpha gene. IL-1alpha promoter constructs drive transcription of the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells, which constitutively produce IL-1alpha. In a cotransfection assay, the Tax protein of both HTLV-I and HTLV-II specifically activated transcription from the IL-1alpha promoter in an uninfected Jurkat cell line. A mutant Tax protein deficient in transactivation of genes by the nuclear factor (NF)-kappaB pathway was unable to induce transcriptional activity of IL-1alpha promoter-CAT constructs, but was rescued by exogenous provision of p65/p50 NF-kappaB. We found that two IL-1alpha kappaB-like sites (positions -1,065 to -1,056 and +646 to +655) specifically formed a complex with NF-kappaB-containing nuclear extract from MT-2 cells and that NF-kappaB bound with higher affinity to the 3' NF-kappaB binding site than to the 5' NF-kappaB site. Moreover, deletion of either 5' or 3' NF-kappaB sites reduced IL-1alpha promoter activity in MT-2 cells and transactivation of the IL-1alpha promoter by exogenous NF-kappaB and Tax in Jurkat cells. These data suggest a general role for Tax induction of IL-1alpha gene transcription by the NF-kappaB pathway. Expression of IL-1alpha by HTLV-I productively infected cells may be important in the hypercalcemia, osteolytic bone lesions, neutrophilia, elevation of C-reactive protein, and fever frequently seen in patients with HTLV-I-induced adult T-cell leukemia/lymphoma.
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PMID:Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins. 860 59

The serum concentration of oncostatin M (OSM) was measured in 40 multiple myeloma patients at diagnosis. Serum OSM level exceeded the sensitivity limit of the ELISA assay in eight (20%) of these patients (OSM+ patients). The serum levels of IL-6, another member of the gp180 cytokine family and C-reactive protein (CRP) as a surrogate of IL-6 were significantly higher in OSM+ patients. There was a trend towards higher serum beta 2M concentration in OSM+ patients, whereas there was no difference in the serum sIL-6R level or clinical data (age, gender, myeloma protein or stage) between the two groups. Two human myeloma cell lines secreted OSM and IL-6, but not IL-11 or leukaemia inhibitory factor (LIF), which suggests an important role for OSM and IL-6 in supporting growth of myeloma cells.
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PMID:Serum oncostatin M in multiple myeloma: association with prognostic factors. 901 1

In 93 newly diagnosed lymphoma patients, tumor necrosis factor alpha (TNF alpha) and its p55 soluble receptor (p55-sR), were prospectively determined in plasma by IRMA and ELISA methods respectively. These 93 patients included 31 patients with low grade lymphoma, 55 with intermediate or high grade lymphoma and 7 with Hodgkin's disease. Median TNF alpha plasma values were 20 pg/mL (range 5-380 pg/mL) in patients versus 7 pg/mL (range 4-9 pg/mL) in healthy control subjects. Presence of TNF alpha level equal or greater than 20 pg/mL was significantly associated with elevated LDH level, serum beta 2-microglobulin level > or = 3 mg/L, hemoglobin < or = 12 g/dL, Ann Arbor stage III or IV disease, and with bulky tumor. High level of TNF alpha was also associated, although less strongly, with B symptoms, poor performance status, and serum albumin < or = 35 g/L, yet it was not associated with change in acute phase protein levels. Levels of p55-sR were also markedly elevated in these lymphoma patients (median of 3.5 ng/mL, range 0.8-18.8 ng/mL) versus 1.45 ng/mL in control subjects (range 1.1-2.3 ng/mL). Level of p55-sR equal or greater than 3.5 ng/mL was significantly associated with poor performance status, B symptoms, beta 2-microglobulin levels > or = 3 mg/L, serum albumin < or = 35 g/L, C-reactive protein > 6 mg/L, hemoglobin < or = 12 g/dL, and bulky tumor. In the whole group of 93 patients, both high TNF alpha and p55-sR levels strongly predicted short freedom from progression and overall survival. This study suggests that elevated TNF alpha and p55-sR plasma levels have a high correlation with other adverse prognostic factors in lymphoma patients and predict their poor outcome.
Leukemia 1997 Apr
PMID:Prognostic significance of TNF alpha and its p55 soluble receptor in malignant lymphomas. 920 18

We have investigated the function of different mediators of the regulation of the human C-reactive protein (hCRP) gene in transgenic mice. hCRP was induced by lipopolysaccharide and wounding in interleukin-6 (IL-6) +/+ mice, but not in IL-6 -/- mice. This finding suggested that IL-6 is necessary for the induction of hCRP. However, injection of IL-6 did not induce the hCRP gene. Thus, the induction of hCRP by IL-6 seems to require an additional cofactor. Therefore, we screened different cytokines for their activity in IL-6 +/+ and IL-6 -/- mice. Surprisingly, interleukin-1beta, as well as oncostatin M or leukaemia inhibitory factor, led to an induction of hCRP in both genetic backgrounds. These results indicate an IL-6-dependent and -independent regulation of hCRP. These hCRP transgenic mice therefore represent a novel model system for defining the cytokine network involved in the regulation of acute-phase genes during the course of inflammation.
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PMID:Interleukin-6-dependent and -independent regulation of the human C-reactive protein gene. 935 11

We measured the circulating levels of interleukin (IL)-6 in adult T-cell leukaemia/lymphoma (ATL) patients using an enzyme-linked immunosorbent assay. The IL-6 levels in 59 ATL patients (median 8.2 pg/ml; range < 1.0 to 185.7 pg/ml) were significantly higher than in 30 healthy controls (median < 1.0 pg/ml; range < 1.0 to 3.5 pg/ml) (P < 0.0001) or 32 human T-lymphotropic virus type-I (HTLV-I) carriers (median 4.2 pg/ml: range < 1.0 to 13.3 pg/ml) (P = 0.002). Among the ATL patients, the IL-6 levels in the acute- or lymphoma-type patients were significantly higher than those in the chronic-type patients (P < 0.0001). The IL-6 levels were also higher in the patients with B symptoms than in those without B symptoms (P = 0.039), and were significantly correlated with increased serum lactate dehydrogenase (LDH) (P = 0.0004) and C-reactive protein (CRP) (P < 0.0001) and decreased serum albumin (P = 0.0003) values. The patients with elevated IL-6 levels had inferior overall survival periods compared to those with normal IL-6 levels (P = 0.025). ATL is a single disease entity, although its clinical features are quite diverse; the increased production of cytokines may cause the diversity of clinical features. The results of our study indicate that IL-6 is one such cytokine.
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PMID:Circulating interleukin-6 levels are elevated in adult T-cell leukaemia/lymphoma patients and correlate with adverse clinical features and survival. 945 Aug 1

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.
Leukemia 1998 Jul
PMID:In vitro excess ammonia production in human myeloma cell lines. 966 3

Hepatosplenic candidiasis following granulocytopenic periods is a relatively recently recognised problem in immunocompromised patients, particularly in those with acute leukaemia. We present three patients in whom diagnosis of hepatosplenic candidiasis was suspected on the basis of ultrasonographic (US), computed tomographic (CT) findings and confirmed by laparoscopy and biopsy of liver lesions. All three patients were successfully treated briefly with amphotericin B, followed by a longer period of fluconazole. In one patient laparotomy and surgical evacuation of abscesses was performed. This condition could be more often recognised by careful follow-up of liver function test, C-reactive protein level, ultrasonography, CT and MRI after recovery from chemotherapy-induced neutropenia.
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PMID:Hepatosplenic candidiasis after neutropenic phase of acute leukaemia. 1045 63

Interleukin 11 (IL-11) is a pleiotropic cytokine with biological activities on many different cell types. Recombinant human IL-11 (rhIL-11) is produced by recombinant DNA technology in Escherichia coli. Both in vitro and in vivo, rhIL-11 has shown effects on multiple hematopoietic cell types. Its predominant in vivo hematopoietic activity is the stimulation of peripheral platelet counts in both normal and myelosuppressed animals. This activity is mediated through effects on both early and late progenitor cells to stimulate megakaryocyte differentiation and maturation. rhIL-11 has been approved for the treatment of chemotherapy-induced thrombocytopenia. The hematopoietic effects of rhIL-11 are most likely direct effects on progenitor cells and megakaryocytes in combination with other cytokines or growth factors. rhIL-11 also induces secretion of acute phase proteins (ferritin, haptoglobin, C-reactive protein, and fibrinogen) from the liver. The induction of heme oxidase and inhibition of several P450 oxidases have been reported from in vitro studies. In vivo, rhIL-11 treatment decreases sodium excretion by the kidney by an unknown mechanism and induces hemodilution. rhIL-11 also exhibits anti-inflammatory effects in a variety of animal models of acute and chronic inflammation, including inflammatory bowel disease, inflammatory skin disease, autoimmune joint disease, and various infection-endotoxemia syndromes. rhIL-11 has trophic effects on non-transformed intestinal epithelium under conditions of mucosal damage. The mechanism of the anti-inflammatory activity of rhIL-11 has been extensively studied. rhIL-11 directly affects macrophage and T cell effector function. rhIL-11 inhibits tumor necrosis factor-alpha (TNF alpha), interleukin 1beta (IL-1beta), interleukin 12 (IL-12), interleukin 6 (IL-6), and nitric oxide (NO) production from activated macrophages in vitro. The inhibition of cytokine production was associated with inhibition of nuclear translocation of the transcription factor, nuclear factor kappa B (NF-kappaB). The block to NF-kappaB nuclear translocation correlates with the ability of rhIL-11 to maintain or enhance production of the inhibitors of NF-kappaB, IkappaB-alpha and IkappaB-beta. In addition to effects on macrophages, rhIL-11 also reduces CD4+ T cell production of Th1 cytokines, such as IFN gamma induced by IL-12, while enhancing Th2 cytokine production. rhIL-11 also blocks IFN gamma production in vivo. The molecular effects of rhIL-11 have also been studied in a clinical trial. Molecular analysis of skin biopsies of patients with psoriasis before and during rhIL-11 treatment demonstrates a decrease in mRNA levels of TNF alpha, IFN gamma and iNOS. These activities suggest that in addition to its thrombopoietic clinical use, rhIL-11 may also be valuable in the treatment of inflammatory diseases. The clinical utility of the anti-inflammatory properties of rhIL-11 is being investigated in patients with Crohn's disease, psoriasis and rheumatoid arthritis. These diseases are believed to be initiated and maintained by activated CD4+ Th1 cells in conjunction with activated macrophages.
Leukemia 1999 Sep
PMID:Hematopoietic, immunomodulatory and epithelial effects of interleukin-11. 1048 79

It is known that alkylating agents and topoisomerase II inhibitors can cause distinct forms of therapy-related leukemia and myelodysplastic syndrome (TRL/MDS). Although several reports have been made on each of these agents separately, no study has yet been conducted to evaluate the effect of these two types of agents in the same population. In a nationwide, large-scale population study, the clinical and cytogenetic features as well as the prognostic factors in 256 patients with TRL/MDS were assessed. Median age was 61 years, and the median period of latency from primary malignancies was 47.9 months. The latency period was significantly shorter in patients undergoing chemotherapy, especially that of topoisomerase II inhibitors, for primary cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia in 59% and MDS in 41% of patients. Chromosome abnormalities that frequently involved chromosomes 5, 7 or 11 were documented in 77% of the 189 patients examined. MLL gene rearrangements were detected in 11 of 58 subjects and were correlated with a borderline significance (P = 0.072) with topoisomerase II inhibitor administration. Overall median survival was only 9.7 months. Survival was similar in cases with or without MLL gene rearrangement. Multivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, poor therapy outcomes for primary cancer, C-reactive protein, and thrombocytopenia as being significantly poor prognostic factors (P < 0.05). This large-population study provided a comprehensive update of TRL/MDS status in Japan, identified significant prognostic factors, and enabled the clinical significance of MLL gene rearrangement to be assessed.
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PMID:Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors. 1074 24


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