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

The leptin receptor is a member of the cytokine receptor superfamily, and is expressed in CD34 haemopoietic stem cells. We examined expression of the leptin receptor in fresh human leukaemia cells. Northern blot analysis showed the leptin receptor was expressed in leukaemic cells from patients with acute myeloblastic leukaemia, acute lymphoblastic leukaemia and chronic myeloid leukaemia (CML). In CML, higher expression was observed in blast crisis than in chronic phase. The expression of leptin receptor decreased during in vitro differentiation of leukaemic blast cells. It appeared that expression of the leptin receptor was associated with immature leukaemic blast cells. Our findings may indicate the possibility that leptin has some role in leukaemia.
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PMID:Expression of the leptin receptor in human leukaemic blast cells. 972 1

Thrombopoietin (TPO) is a primary regulator of megakaryopoiesis and thrombopoiesis, and has recently been identified as the ligand for the cytokine receptor MPL. Several lines of evidence suggest that dysregulation of MPL expression or TPO production are implicated in the pathogenesis of various myeloproliferative disorders. For example, mutations in the MPL gene can cause factor-independent growth and a transformed phenotype in vivo, and MPD may be associated with altered expression of the MPL receptor or TPO. Blast cells from patients with acute myelogenous leukemia (AML) often display MPL, and TPO induces some of these to proliferate. In sum, MPL may play a role as part of an autocrine pathway of MPD. While much remains to be clarified about the therapeutic use of TPO in AML, early results suggest it may be useful for platelet donation and/or priming to alleviate chemotherapy-induced thrombocytopenia in other malignant conditions.
Leukemia 1998 Sep
PMID:The role of the MPL receptor in myeloproliferative disorders. 977 96

We have studied the expression of cytokine receptors CD25 (IL-2Ra,55kD), CD116 (hGM-CSRF,145kD), CD117 (CSFR,145kD), CD120a (TNFR,55kD), CD120b (TNFR,75kD), CD121a (IL-1R, type I, 80kD), CD123 (IL-3R), CD124 (IL-4R, 140kD), CD126 (IL-6R, 80kD), CDw127 (IL-7R, 75kD), CDw128 (IL-8R), CD130 (gp130 subunit), CD131 (common beta), CD134 (OX40) and also CD95 (Fas antigen) on the myeloid leukemic cells. Cells from peripheral blood or bone marrow of 30 patients with disorders in myeloid lineage included mostly acute myeloid leukemias (with high leukocyte count and percentage of blasts) were analyzed for the expression of surface membrane molecules by indirect immunofluorescence method evaluated by flow cytometry. The findings indicate that some monoclonal antibodies have a reactivity against cytokine receptors of pathological cells in individual cases, but with very variable qualitative and quantitative (number copies/cell) expression (preliminary results). The leukemic cells demonstrate unique cytokine receptor profiles, which reveal the great diversity of immunophenotypes within the main functional characterization of blood malignancies. The immunophenotype heterogeneity of leukemic cells has proved to be much greater than to match with existing classification criteria. This fact could raise the necessity of further evaluation and specification of cytokine markers of the myeloid acute leukemias. On the other hand, detection of cytokine receptors on the leukemia cells is important for cytokine therapy.
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PMID:Expression of cytokine receptors on different myeloid leukemic cells. 989 Jun 61

Primary effusion lymphoma (PEL) is a new lymphoma entity occurring predominantly, but not exclusively in HIV+ patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. The cells are infected with the newly discovered human herpesvirus-8 (HHV-8), often accompanied by co-infection with Epstein-Barr virus (EBV). Several lymphoma cell lines have been established from patients with AIDS- and non-AIDS-associated PEL. Given their phenotypical relationship to plasma cells, several cytokines may be important for growth and survival of PEL cells. We investigated the spectrum of cytokines produced by nine HHV-8+ PEL cell lines, in comparison with five Burkitt lymphoma, seven other B non-Hodgkin's lymphoma (B-NHL) and seven multiple myeloma-derived cell lines. In addition, we tested the response of the PEL cells to selected cytokines and the effects of neutralizing anti-cytokine and anti-cytokine receptor antibodies. Using specific ELISAs, PEL cell lines were found to produce large amounts of interleukin-6 (IL-6; 10-5000 pg/ml), IL-6 soluble receptor (IL-6sR; 30-600 pg/ml), IL-10 (600-80,000 pg/ml) and oncostatin M (OSM; 50-80 pg/ml) which in most cases were significantly higher than the levels produced by the Burkitt, B-NHL or myeloma cell lines; on the contrary, PEL cell lines did not elaborate significant levels of macrophage inhibitory protein (MIP-1alpha) and leukemia inhibitory factor (LIF). However, the levels of MIP-1alpha were increased 10- to 100-fold by treatment with phorbol ester TPA. PEL cell lines did not respond proliferatively to IL-6, IL-10, IL-11, LIF, MIP-1alpha, or OSM. Incubation with IL-6sR and IL-6 inhibited cell growth. Anti-IL6 neutralizing antibodies had no effect on PEL cell line proliferation; conversely, whereas anti-IL6R alone inhibited only weakly, anti-gp130 and anti-gp130 plus anti-IL6R showed strong inhibitory effects (>20% inhibition in 5/9 lines and >60% inhibition in 3/9 lines). In summary, PEL cell lines produce high amounts of cytokines (IL-6, IL-10, OSM); proliferation could be inhibited by blocking the receptors of the IL-6 signaling pathway.
Leukemia 1999 Apr
PMID:Constitutive cytokine production by primary effusion (body cavity-based) lymphoma-derived cell lines. 1021 73

To determine activation status of the IL-2R-associated (Jak/STAT) pathway in the HTLV-I infected cells, we examined tyrosine phosphorylation of Jak3, STAT3, and STAT5 in several HTLV-I(+) T-cell lines and in uncultured leukemic T cells isolated from patients with adult T-cell lymphoma/leukemia (ATLL). Constitutive basal phosphorylation of Jak3 and, usually, STAT3 and STAT5 was detected in all four IL-2-independent cell lines tested, but in none of the three IL-2-dependent cell lines. Similarly, there was no detectable basal phosphorylation of Jak3 and STAT5 in the leukemic cells from ATLL patients (0/8 and 0/3, respectively). However, stimulation with IL-2 resulted in Jak3 and STAT5 phosphorylation in both leukemic ATLL cells and IL-2-dependent lines. Furthermore, expression of SHP-1 phosphatase which is a negative regulator of cytokine receptor signaling, was lost in most IL-2 independent cell lines (3/4) but not in the leukemic ATLL cells (0/3). Finally, the HTLV-I(+) T-cell lines (313) but not the control, HTLV-I(-) T-cell lines were resistant to rapamycin and its novel analog RAD. We conclude that (1) HTLV-I infection per se does not result in a constitutive phosphorylation of the Jak3, STAT3, and STAT5 proteins; (2) malignant transformation in at least some cases of ATLL does not require the constitutive, but may require IL-2-induced, activation of the IL-2R Jak/STAT pathway; and (3) there are major differences in T-cell immortalization mechanism(s) which appear to involve SHP-1 and target molecules for rapamycin and RAD.
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PMID:Differences in phosphorylation of the IL-2R associated JAK/STAT proteins between HTLV-I(+), IL-2-independent and IL-2-dependent cell lines and uncultured leukemic cells from patients with adult T-cell lymphoma/leukemia. 1022 24

Members of the JAK family of protein tyrosine kinase (PTK) proteins are required for the transmission of signals from a variety of cell surface receptors, particularly those of the cytokine receptor family. JAK function has been implicated in hematopoiesis and regulation of the immune system, and recent data suggest that the vertebrate JAK2 gene may play a role in leukemia. We have isolated and characterized jak cDNAs from the zebrafish Danio rerio. The zebrafish genome possesses 2 jak2 genes that occupy paralogous chromosome segments in the zebrafish genome, and these segments conserve syntenic relationships with orthologous genes in mammalian genomes, suggesting an ancient duplication in the zebrafish lineage. The jak2a gene is expressed at high levels in erythroid precursors of primitive and definitive waves and at a lower level in early central nervous system and developing fin buds. jak2b is expressed in the developing lens and nephritic ducts, but not in hematopoietic tissue. The expression of jak2a was examined in hematopoietic mutants and found to be disrupted in cloche and spadetail, suggesting an early role in hematopoiesis. Taken together with recent gene knockout data in the mouse, we suggest that jak2a may be functionally equivalent to mammalian Jak2, with a role in early erythropoiesis.
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PMID:Gene duplication of zebrafish JAK2 homologs is accompanied by divergent embryonic expression patterns: only jak2a is expressed during erythropoiesis. 1051 66

Erythropoietin (Epo)-independent differentiation of erythroid progenitors is a major characteristic of myeloproliferative disorders, including chronic myeloid leukemia. Epo receptor (EpoR) signaling is crucial for normal erythroid development, as evidenced by the properties of Epo(-/-) and EpoR(-/-) mice, which contain a normal number of fetal liver erythroid progenitors but die in utero from a severe anemia attributable to the absence of red cell maturation. Here we show that two constitutively active cytoplasmic protein tyrosine kinases, P210(BCR-ABL) and v-SRC, can functionally replace the EpoR and support full proliferation, differentiation, and maturation of fetal liver erythroid progenitors from EpoR(-/-) mice. These protein tyrosine kinases can also partially complement the myeloid growth factors IL-3, IL-6, and Steel factor, which are normally required in addition to Epo for erythroid development. Additionally, BCR-ABL mutants that lack residues necessary for transformation of fibroblasts or bone marrow cells can fully support normal erythroid development. These results demonstrate that activated tyrosine kinase oncoproteins implicated in tumorigenesis and human leukemia can functionally complement for cytokine receptor signaling pathways to support normal erythropoiesis in EpoR-deficient cells. Moreover, terminal differentiation of erythroid cells requires generic signals provided by activated protein tyrosine kinases and does not require a specific signal unique to a cytokine receptor.
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PMID:BCR-ABL and v-SRC tyrosine kinase oncoproteins support normal erythroid development in erythropoietin receptor-deficient progenitor cells. 1055 95

Implantation is a process that involves development, attachment and invasion of the blastocyst into the endometrium. Successful implantation requires appropriate communication between the embryo and maternal endometrium. There is evidence to suggest that cytokines produced by the maternal endometrium and the developing embryo play a crucial role in this signalling process. Although numerous cytokine-receptor pairs are expressed by the maternal endometrium and the embryo during implantation, functional knowledge of these cytokines is limited. Compelling data demonstrating a functional role for cytokines in implantation comes from studies using specific cytokine and cytokine receptor knockout mice. There are limited similar data for human implantation, but clinical correlative data and studies using in vitro models indicate that cytokines may have an important functional role in this process. Cytokines that appear to have a functional role in mammalian implantation include leukaemia inhibitory factor, interleukin 1, hepatocyte growth factor, stem cell factor, macrophage colony-stimulating factor and insulin-like growth factors. As implantation failure is a significant cause of natural and in vitro fertilization pregnancy failure, a better understanding of the functional role of these cytokine-receptor pairs is important for improving the diagnosis and treatment of infertility.
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PMID:Cytokines in implantation. 1088 32

Hematopoietic cell growth and differentiation are controlled by a number of cytokines. Ligand stimulation induces rapid phosphorylation of the tyrosine residues of the cytokine receptor and a variety of cellular molecules. Among them, Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have recently been found to play a unique role in cytokine receptor-mediated intracellular signaling and hematopoietic cell development. Abnormal signaling of the JAK-STAT pathway results in hematopoietic disorders, including severe combined immunodeficiency and leukemia.
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PMID:Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) in hematopoietic cells. 1090 49

We analysed the regulation of G1-phase progression in relation to cytokine receptor signalling in HepG2 hepatoma cells, stably transduced with the IL-10 receptor after stimulation with Oncostatin M (OSM), IL-6, Leukaemia Inhibitory Factor (LIF) and IL-10. All cytokines induced STAT3 phosphorylation to approximately the same level, but only OSM, and to a lesser extent IL-6, induced STAT5 phosphorylation. The cytokines also stimulated phosphorylation of ERK in the order of decreasing effectiveness: OSM > IL-6 > LIF > IL-10. The same order of activity of the cytokines was observed on inhibition of DNA synthesis and accumulation of cells in the G1-phase of the cell cycle. These processes were accompanied by a decrease in cyclin A expression and CDK2 activity, and enhanced accumulation of p27kip1. The level of p27kip1 mRNA expression was unaffected by the cytokines, and maintenance of the elevated level of p27kip1 occurred independently of de novo protein synthesis. Furthermore, inhibition of proteasomal activity increased the level of p27kip1 in the unstimulated cells to the same level as in OSM-treated cells. Inhibition of MEK activation completely abrogated OSM and IL-6 induced p27kip1 accumulation, while expression of dominant negative STAT5 decreased the OSM and IL-6 mediated inhibition of DNA-synthesis and partially inhibited p27kip1 accumulation.
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PMID:Oncostatin M and interleukin 6 inhibit cell cycle progression by prevention of p27kip1 degradation in HepG2 cells. 1095 74


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