Abstract:
OBJECTIVES:Mantle cell lymphoma (MCL) is an incurable disease with an aggressive course and novel treatment strategies are urgently needed. The purpose of this study was to evaluate the effects of histone deacetylase (HDAC) inhibitors, a new group of antiproliferative agents, on human MCL cells. METHODS:Three MCL cell lines (JeKo-1, Hbl-2 and Granta-519) were exposed to different concentrations of the HDAC inhibitors sodium butyrate (NaB) and suberoylanilide hydroxamic acid (SAHA) for 8-72 h. Their effects on cell viability, apoptosis induction and cell cycle proliferation were studied. Moreover, the influence of SAHA on the expression of cyclin D1, the cell cycle regulators p21 and p27 and the production of vascular endothelial growth factor (VEGF) were analyzed. RESULTS:The HDAC inhibitors induced accumulation of acetylated histones in MCL cells. MTT assays and Annexin-V staining showed that they potently inhibited viability in a dose-dependent manner and induced apoptosis in all cell lines tested. Cell cycle analysis indicated that their exposure to SAHA or NaB decreased the proportion of cells in S phase and increased the proportion of cells in the G0/G1 and/or G2/M phases. Incubation with the two HDAC inhibitors resulted in downregulation of cyclin D1. SAHA lead to an upregulation of p21 in all cell lines and an upregulation of p27 in JeKo-1 and Granta-519 cells, while expression of p27 in Hbl-2 was not altered. In addition, SAHA inhibited the production of the angiogenic cytokine VEGF. Treatment with NaB increased the expression of p21 in JeKo-1 and Hbl-2 cells, while in Granta 519 cells no effect was noted. The expression of p27 remained constant in all three cell lines after exposure to NaB. CONCLUSION:Based on these findings, we provide evidence that HDAC inhibitors have antiproliferative effects in MCL and may represent a promising therapeutic approach.
journal_name
Eur J Haematoljournal_title
European journal of haematologyauthors
Heider U,Kaiser M,Sterz J,Zavrski I,Jakob C,Fleissner C,Eucker J,Possinger K,Sezer Odoi
10.1111/j.1600-0609.2005.00546.xsubject
Has Abstractpub_date
2006-01-01 00:00:00pages
42-50issue
1eissn
0902-4441issn
1600-0609pii
EJH546journal_volume
76pub_type
杂志文章abstract::Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, and high-dose dexamethasome (HD-DXM) has been used as a first-line therapy for patients with ITP. However, little is known about the role of dendritic cells (DCs) and CD4(+)Foxp3(+) regulatory T (Treg) cells in the pathogenesis of chronic ITP and the eff...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.2007.00917.x
更新日期:2007-10-01 00:00:00
abstract::GM-CSF may induce pulmonary complications, such as dyspnea with temporary decreases in oxygen saturation described as first dose effect for higher dosages of intravenous rhGM-CSF. This study investigated possible pulmonary disturbances in adult de novo AML patients receiving yeast rhGM-CSF 24 h prior to chemotherapy u...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1997.tb01689.x
更新日期:1997-11-01 00:00:00
abstract::Propagation of the vaso-occlusive process in sickle cell anaemia (SCA) is a complex process involving the adhesion of steady-state SCA patients red cells and reticulocytes to the vascular endothelium. The effect of hydroxyurea therapy (HUT) on the adhesive properties of sickle cells and the expression of adhesion mole...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2006.00788.x
更新日期:2007-02-01 00:00:00
abstract::The new World Health Organization (WHO) classification of hematologic malignancies has incorporated t(8;21) myelodysplastic syndromes (MDS) according to the French-American-British classification into the category of acute myeloid leukemia (AML) with t(8;21)(q22;q22), while our knowledge about clinicopathological feat...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2002.02770.x
更新日期:2002-09-01 00:00:00
abstract::Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variability in a population....
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0609.2011.01700.x
更新日期:2012-01-01 00:00:00
abstract::Interferon (IFN) is one of several drugs effective in treating multiple myeloma (MM), and propagermanium is an IFN inducer. We report on 10 MM patients who were treated with propagermanium at doses from 10 to 40 mg. Two patients achieved complete remission (CR), two patients achieved partial remission (PR), and the co...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.2004.00330.x
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVES:Iron-overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. However, the precise mechanisms of iron entry and sequestration in the heart are still unclear. Our previous study showed that Fe(2+) uptake in thalassemic cardiomyocytes are mainly mediated by T-type calci...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2012.01779.x
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVES:Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, an...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12850
更新日期:2017-05-01 00:00:00
abstract::To determine if mutations of the Wilms' tumor predisposing gene (WT1) are associated with haematological malignancies, we have investigated 65 cases of acute leukaemia, including 39 patients in blast crisis of chronic myeloid leukaemia (CML), by amplification of WT1 exons 7, 8 and 9 followed by single-strand conformat...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1997.tb01681.x
更新日期:1997-05-01 00:00:00
abstract:INTRODUCTION:Lower risk myelodysplastic syndromes (MDSs) are characterised by increased apoptosis of haematopoietic cells in the bone marrow (BM). The mechanism driving this excessive apoptosis involves multiple immune molecules, including inflammatory cytokines such as interferon-γ (IFN-γ), tumour necrosis factor-α (T...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12074
更新日期:2013-05-01 00:00:00
abstract::Myeloproliferative neoplasms associated with FIP1L1-PDGFR rearrangements represent a rare subset of myeloid and lymphoid malignancies, characterised by the presence of eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 genes. The fusion product of such genes is a tyrosine kinase oncoprotein sensitive to imatini...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12272
更新日期:2014-06-01 00:00:00
abstract::The European LeukemiaNet (ELN) is composed of several work packages, four of them being directly involved in the various aspects of diagnosis. On the occasion of the annual ELN meeting of 2015 in Mannheim, these four work packages collectively examined the current situation and future prospects of cytomorphology, flow...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/ejh.12603
更新日期:2015-10-01 00:00:00
abstract::MALT lymphoma is usually described in association with Helicobacter pylori, HCV, HHV8, Campylobacter jejuni or in a setting of overreactive immunity. In HIV(+) patients, MALT lymphoma is most commonly described in children. We describe here an original case of HIV(+) MALT lymphoma with bronchial, conjuctival and laryn...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2004.00339.x
更新日期:2005-01-01 00:00:00
abstract::CD200R is an inhibitory receptor involved in the regulation of myeloid cells. It recruits Dok-1 and Dok-2, which are potent inhibitors of the Ras signalling pathway used by colony-stimulating factor (CSF) receptors. Dok-1/Dok-2 double knockout (DKO) mice develop leukaemia at 10-12 months of age. We investigated whethe...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00920.x
更新日期:2007-11-01 00:00:00
abstract::The molecular defects of the factor XIII A subunit gene were studied in a patient with factor XIII deficiency. Mutation analysis was performed on amplified DNA from each exon of this gene by single-strand conformation polymorphism (SSCP) and DNA sequencing techniques. A substitution of guanine by adenine at nucleotide...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2000.065004279.x
更新日期:2000-10-01 00:00:00
abstract::Externalization of phosphatidylserine (PS) is thought to contribute to sickle cell disease (SCD) pathophysiology. The red blood cell (RBC) aminophospholipid translocase (APLT) mediates the transport of PS from the outer to the inner RBC membrane leaflet to maintain an asymmetric distribution of PL, while phospholipid ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12506
更新日期:2015-11-01 00:00:00
abstract::The cycling rate of haemopoietic stem cells (day 9 CFU-S) and granulocyte-macrophage colony forming cells (GM-CFC) in mouse femora was, in response to reduced numbers, elevated at all times of sampling between 3 weeks and 10 months after 4 repeated doses of 4.5 Gy X-rays (3 wk between doses). The level of a stimulator...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb01193.x
更新日期:1988-09-01 00:00:00
abstract:OBJECTIVES:Granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation (HSCT) provides a valuable and increasingly used alternative to bone marrow transplantation (BMT). This retrospective study aimed at determining whether the stem cell source is predictive for outcome, rel...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2011.01692.x
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVES:Hypocholesterolemia has been previously described in patients affected by thalassemia. In this study we retrospectively evaluated the cholesterol level in two groups of patients affected by either thalassemia major (TM) or thalassemia intermedia (TI), with the aim of establishing factors correlated to hypoch...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2008.01195.x
更新日期:2009-03-01 00:00:00
abstract::Human red blood cells (RBC) are heterogeneous with respect to their size; the physiological significance of this heterogeneity has not yet been fully elucidated. To further investigate this problem, some characteristics of human RBC fractionated according to their mean corpuscular volume (MCV) by counterflow centrifug...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1992.tb00570.x
更新日期:1992-02-01 00:00:00
abstract:OBJECTIVES:Human Disabled-2 (Dab2), a putative tumor suppressor gene, is frequently down-regulated in human tumors. This study aims to explore the association between Dab2 methylation status and expression in newly diagnosed myelodysplastic syndrome (MDS) patients and patients who received 5-aza-2'-deoxycytidine (decit...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12014
更新日期:2012-12-01 00:00:00
abstract::The association of infectious mononucleosis and an immunocompromised host such as occurs in acute leukemia is reported. The most common cause of infectious mononucleosis is Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Patients with mononucleosis syndrome caused by other agents are rare. We report a case of acut...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2002.01647.x
更新日期:2002-04-01 00:00:00
abstract::Sickle cell disease (SCD) is an inherited disorder secondary to a point mutation at the sixth position of the beta chain of human hemoglobin resulting in the replacement of valine for glutamic acid. This recessive genetic abnormality precipitates the polymerization of the deoxygenated form of hemoglobin S inducing a m...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/ejh.12447
更新日期:2015-05-01 00:00:00
abstract::Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm, characterized by persistent monocytosis. Due to the lack of unique surface markers expressed by neoplastic monocytes and the frequent CD34-negative blast immunophenotype, the diagnostic value of flow cytometric immunophenotyping (...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12477
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVES:An aberrant pattern of expression of L-selectin and intercellular adhesion molecule 1 (ICAM1) may characterise CD34+ blast cells in myelodysplastic syndromes (MDS) and secondary acute myeloid leukaemia (sAML). METHODS:In a three-colour flow cytometric assay, we evaluated the expression of L-selectin and ICA...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00986.x
更新日期:2008-02-01 00:00:00
abstract::Cells from 3 patients with B-chronic lymphocytic leukaemia (B-CLL) and 1 with B-prolymphocytic leukaemia (B-PLL) were treated in vitro with the phorbol ester 12-0-tetradecanoylphorbol (TPA), the calcium ionophore A23187, or a combination of TPA and A23187. TPA induced the cells to adhere to the culture flask or to clu...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb01189.x
更新日期:1988-09-01 00:00:00
abstract::This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2-yr disease-free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the ...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/ejh.12038
更新日期:2013-02-01 00:00:00
abstract:OBJECTIVES:On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. METHODS:Data were obtained from the EORTC20981 t...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12264
更新日期:2014-01-01 00:00:00
abstract::In March 1981, a 53-year-old man presented with itching and was diagnosed as having myelofibrosis. There was gradual enlargement of the spleen over the following 5 yr. His spleen had to be removed in February 1986 because of physical discomfort. 3 months post-splenectomy he became polycythaemic. Bone marrow examinatio...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1989.tb00254.x
更新日期:1989-01-01 00:00:00
abstract::It has been reported that in vitro prednisolone (PDN) resistance provides a prognostic value in childhood acute lymphoblastic leukaemia (ALL). This study aimed at investigating the biological and clinical significance of in vitro PDN resistance in adult ALL. Blast cells from 30 patients were exposed to PDN (0.1 microM...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1996.tb01351.x
更新日期:1996-08-01 00:00:00