Abstract:
:The cytokine IL-6 has been proposed as an autocrine growth factor in multiple myeloma, and is also required for stimulation of immunoglobulin production and secretion in normal plasma cells and myeloma cells. In this study, we showed that secreted IL-6 is detectable by Western blot analysis in a panel of lymphoid and myeloma cell lines. Previous studies in our laboratory have shown that dexamethasone and suramin inhibit cell proliferation and IL-6-mediated immunoglobulin secretion in various lymphoblastoid and myeloma cell lines. In the present study, we present study, we present data to examine mechanisms by which dexamethasone and suramin inhibit IL-6-mediated immunoglobulin secretion in the lymphoid cell line SKW 6.4. Cells treated with rIL-6 or the IC10 concentration of dexamethasone respectively undergo a doubling of intracellular IgM. Moreover, rIL-6 and dexamethasone additively stimulate cells to accumulate intracellular IgM. In contrast, cells treated with the IC10 concentration of suramin undergo no significant alteration of total cellular IgM, and do not respond to IL-6 with an increase in intracellular IgM. Northern blot analysis demonstrates that cells treated with exogenous rIL-6 and/or dexamethasone respectively undergo a coordinate one to three fold increase of kappa and mu chain mRNA expression, while there is a 30-40% decrease of kappa and mu chain mRNA when cells are treated with suramin and suramin plus rIL-6. Western blot analysis shows that levels of intracellular IL-6 modestly increase when cells are treated with exogenous rIL-6, whereas treatment with dexamethasone plus rIL-6 causes a 70% decrease of immunoreactive IL-6 protein in comparison with untreated cells. An rtPCR analysis of IL-6 mRNA expression shows an abolished signal in response to dexamethasone or rIL-6 and/or dexamethasone. Using a flow cytometric assay, it is demonstrated that suramin inhibits IL-6 binding to its receptor. Taken together, these results indicate that SKW 6.4 cells treated with rIL-6 and/or dexamethasone undergo increased expression of IgM mRNA leading to increased intracellular IgM levels. Treatment with suramin or suramin plus rIL-6 does not alter the IL-6 protein level or the mRNA levels for IL-6 and IL-6 receptor. Suramin treatment causes a moderate decrease in IgM mRNA, and this is associated with a decreased intracellular level of IgM in SKW 6.4 cells. Overall these findings support the concept that IL-6 is an autocrine factor for immunoglobulin production and secretion in myeloma cells. Suramin interferes with IL-6 binding to its receptor and/or decreases IL-6 receptor expression. Dexamethasone has neither of these effects on IL-6 receptor expression or IL-6 binding to its receptor, and we postulate that it acts through a block in secretion or in degradation of intracellular immunoglobulin by decreasing IL-6 mRNA expression and IL-6 protein content. These studies suggest that the combination of suramin and dexamethasone not only synergistically growth inhibit myeloma cells but also act in concert to inhibit immunoglobulin secretion and represent a therapeutic approach worthy of further investigation.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Shiao RT,McLeskey SB,Khera SY,Wolfson A,Freter CEdoi
10.3109/10428199209067610subject
Has Abstractpub_date
1996-04-01 00:00:00pages
293-303issue
3-4eissn
1042-8194issn
1029-2403journal_volume
21pub_type
杂志文章abstract::The objective of this work was to determine the safety and efficacy of gemtuzumab ozogamicin in patients with poor prognosis acute myeloid leukemia (AML). Patients with the following diagnoses/characteristics were treated with 1-3 infusions of gemtuzumab ozogamicin at a dose of 9 mg/m2: (1) relapse of AML < or = 6 mon...
journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
doi:10.1080/1042819021000016078
更新日期:2002-10-01 00:00:00
abstract::In acute myeloid leukemia (AML), cytogenetics predicts treatment outcome for the favorable and poor subgroups but not for the intermediate subgroup. Polymorphisms within the nucleotide excision repair (NER) pathway may lead to interindividual differences in DNA repair capacity, influencing outcome. We studied the role...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190903582804
更新日期:2010-04-01 00:00:00
abstract::The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eight...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2014.951844
更新日期:2015-05-01 00:00:00
abstract::Human mantle cell lymphoma (MCL) cell lines are scarce and have been only sporadically described and validated, and only a few have been thoroughly molecularly or genetically characterized. We describe here the successful establishment of a new MCL line, PF-1, with typical MCL characteristics. Culturing primary MCL ce...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2014.901511
更新日期:2015-01-01 00:00:00
abstract::Few reports on the successful treatment of T-cell large granular lymphocyte (LGL) leukemia with the humanized anti-CD52 monoclonal antibody alemtuzumab are emerging in the literature. The expression of CD52 by LGLs has not been previously investigated. Using semi-quantitative 2- and 3-color flow cytometry, we document...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190500052156
更新日期:2005-05-01 00:00:00
abstract::Chronic exposure to high concentrations of benzene is associated with an increased incidence of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving loss of all or part of chromosomes 5 and/or 7 as...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199909145730
更新日期:1999-10-01 00:00:00
abstract::In an attempt to better understand the clinicopathologic features of T- and natural killer (NK)/T-cell lymphomas in Taiwan and the distribution and relative frequency of each subtype according to the new WHO classification, the pathology file of a medical center in southern Taiwan during 1989-2002 was retrospectively ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190310001625881
更新日期:2004-05-01 00:00:00
abstract::Infection, relapse, and GVHD can complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the effect of poor immune recovery on infection risk is well-established, there are limited data on the effect of immune reconstitution on relapse and survival, especially following T-cell depletion (TC...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2016.1265113
更新日期:2017-08-01 00:00:00
abstract::The association of chronic lymphocytic leukemia (CLL) with essential thrombocythemia (ET) is an extremely rare event and until now 3 patients with such coexistence have been reported in the literature. We report a 77-year-old white woman in whom these two disorders were diagnosed concomitantly on the basis of peripher...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/1042819031000097348
更新日期:2003-08-01 00:00:00
abstract::Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199909058494
更新日期:1999-08-01 00:00:00
abstract::Until recently, combination chemotherapy with melphalan and prednisone (MP) has remained the most widely accepted treatment option for elderly patients with multiple myeloma (MM). However, since the availability of new and more active drugs, several groups have compared in several phase III trials the efficacy and saf...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428194.2010.530361
更新日期:2011-01-01 00:00:00
abstract::The NK-like family of homeobox genes includes TLX1, TLX3 and NKX2-5, which are ectopically activated in distinct subsets of T-cell acute lymphoblastic leukemia (T-ALL) cells. Here we analysed their effect on the miR-17-92 cluster overexpressed in several types of cancer, including T-ALL. The pri-miR-17-92 polycistron ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190802626632
更新日期:2009-01-01 00:00:00
abstract::Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractor...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2017.1379076
更新日期:2018-06-01 00:00:00
abstract::Lithium is commonly used to treat bipolar affective disorder. It is well known to adversely affect thyroid function, most commonly causing hypothyroidism. Hyperthyroidism is a rare complication. Similarly, total body irradiation (TBI) associated with BMT is well known to affect thyroid function frequently causing hypo...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190310001617286
更新日期:2004-04-01 00:00:00
abstract::In this report a rare case of spontaneous regression of a long-standing chemotherapy resistant low grade non-Hodgkin's lymphoma (NHL) of follicular small cleaved cell type is described. Extensive bulky lymphadenopathy substantially resolved, 7 months before the diagnosis of acute myelomonocytic leukaemia was establish...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199609051631
更新日期:1996-01-01 00:00:00
abstract::Several studies have indicated that age, hemoglobin and serum albumin are among the most important prognostic factors for survival of patients with Waldenstrom's macroglobulinemia (WM). Furthermore, recent data indicate that serum b2-microglobulin may be also significant. The recently proposed International Staging Sy...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190410001687512
更新日期:2004-09-01 00:00:00
abstract::Lymphoid recovery following myeloablative stem cell transplantation (SCT) displays a logistic pattern of exponential growth followed by a plateau. Within this logistic framework, lymphoid recovery is characterized by the parameters R (slope of ascent), a (time of maximal rate of ascent) and K (plateau), the 'steady-st...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2018.1452216
更新日期:2018-12-01 00:00:00
abstract::Myeloproliferative neoplasms (MPNs) are associated with pulmonary hypertension (PH). We studied MPN patients who underwent right-heart-catheterization (RHC) to identify hemodynamic differences between MPN-subtypes. Per RHC, hemodynamics were classified as pre, post or combined pre and post-capillary PH. One-way analys...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2020.1864351
更新日期:2021-01-25 00:00:00
abstract::HMG-CoA Reductase inhibitors (statins) induce apoptosis in acute myeloid leukemia (AML) cells in vitro; however, the concentrations associated with cell death in AML cells are higher than those clinically tolerated during prolonged therapy. We therefore wished to determine whether short exposures to lovastatin might i...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190701760011
更新日期:2008-02-01 00:00:00
abstract::To evaluate its clinical efficacy as well as its biologic safety, human recombinant Erythropoietin (rh-Epo) was given to 19 patients with myelodysplastic syndromes (MDS) in an open non-randomized study. Among the seventeen evaluable patients only two showed an apparent hematologic response to rh-Epo treatment. In thes...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199309147366
更新日期:1993-05-01 00:00:00
abstract::This study evaluated whether measures of psychological well-being, including coping style, are associated with advance care planning (ACP). Data were from the Hematology Communications Study (HEMA-COMM), a prospective observational study of physician-patient communication in patients with hematologic malignancies. ACP...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2011.601474
更新日期:2011-12-01 00:00:00
abstract::An increasing incidence of Pneumocystis jiroveci pneumonia (PCP) in patients with B-cell non-Hodgkin lymphoma (B-NHL) receiving rituximab treatment has been reported. We reviewed patients with B-NHL who underwent chemotherapy from 2004 to 2008 at our institution to identify risk factors for PCP development during and ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2010.506569
更新日期:2010-10-01 00:00:00
abstract::The combination of mitoxantrone (MIT), etoposide (ETP), and cytarabine (Ara-C) (MEC) is a frequently used salvage therapy for acute leukemia, but has been associated with severe myelosuppression. Therefore, we investigated the miniMEC regimen with reduced doses of AraC and MIT. Thirteen ALL and 44 AML patients, all re...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2016.1153087
更新日期:2016-11-01 00:00:00
abstract::Strategies for reversing graft failure (GF) after allogeneic stem cell transplant (SCT) depend on the options available in each situation. GF was reported in 16 Spanish institutions from January 2006 to July 2011. Primary GF was defined as an absolute neutrophil count (ANC) > 0.5 × 10(9)/L not reached by day + 28 afte...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,多中心研究
doi:10.3109/10428194.2014.930849
更新日期:2015-03-01 00:00:00
abstract::Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkin's lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was r...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199709059687
更新日期:1997-10-01 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is an important protein kinase regulating cell survival and apoptosis. To determine whether genetic variations in mTOR are associated with risk of acute lymphoblastic leukemia (ALL) in Chinese children, we genotyped two tag single nucleotide poymorphisms (SNPs) in mTOR (rs2536 ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2011.628062
更新日期:2012-05-01 00:00:00
abstract::A methodology for selection of the CD8 cell subset from the peripheral blood and bone marrow mononuclear cells was developed using anti-T8 (CD8) antibody and magnetic microspheres coated with anti-mouse IgG. Following optimization of antibody:cell binding ratio and microsphere:cell ratios, CD8(+)-cells in the peripher...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199209049825
更新日期:1992-09-01 00:00:00
abstract::Relative risks of treatment-emergent adverse events (TEAEs) and related hospitalization is most accurate when accounting for treatment exposure. AZA-AML-001 showed azacitidine (AZA) prolonged overall survival versus conventional care regimens (CCR) in older patients (≥65 years) with acute myeloid leukemia (AML) by 3.9...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,多中心研究
doi:10.1080/10428194.2016.1243680
更新日期:2017-06-01 00:00:00
abstract::The capacity to generate effective dendritic cells (DC) from adult acute lymphoblastic leukemia (ALL) patients in complete remission (CR) and off-therapy was investigated. Monocyte-derived DC cultured in the presence of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4 and tumor necrosis factor (TNF...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190601101001
更新日期:2007-02-01 00:00:00
abstract::We retrospectively analyzed data of 47 patients aged 60 years or older, hospitalized in our institution with the diagnosis of acute myelogenous leukemia (AML), and searched for prognostic factors. Induction with anthracyclines significantly correlated with better complete remission (CR) rate (P = 0.0016) and overall s...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190210204
更新日期:2002-01-01 00:00:00