Abstract:
:A variety of genetic and epigenetic abnormalities were characterized over the last years in Hodgkin and Reed-Sternberg (H-RS) cells of classic Hodgkin Lymphoma (cHL). It was speculated that simultaneous inhibition of multiple signalling pathways might be a promising strategy to target this tumor entity. In the present study we tested the effect of histone deacetylase (HDAC) inhibition using depsipeptide (also known as romidepsin, FK228, FR901228 or NSC-630176) in cHL cell lines in vitro. Molecular mechanisms of toxicity were analyzed using RNA expression analysis and functional assays. It is shown that depsipeptide is effective at submicromolar concentrations and acts mainly by apoptosis induction, upregulation of p21 and cell cycle inhibition in G2/M. Of special note, HDAC mediated toxicity in H-RS cells does not require RelA/p65 downregulation, which was previously shown to drive the malignant phenotype of H-RS cells. In summary, depsipeptide induced protein acetylation results in transcriptional changes of a large number of pathogenetically relevant genes and increased RelA/p65 binding activity in cHL cell lines. Our preclinical data suggest that HDAC inhibition using depsipeptide might be a promising approach for the treatment of cHL patients.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Hartlapp I,Pallasch C,Weibert G,Kemkers A,Hummel M,Re Ddoi
10.1016/j.leukres.2008.12.013subject
Has Abstractpub_date
2009-07-01 00:00:00pages
929-36issue
7eissn
0145-2126issn
1873-5835pii
S0145-2126(08)00563-8journal_volume
33pub_type
杂志文章abstract::Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondria. Within 10m...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.07.009
更新日期:2009-01-01 00:00:00
abstract::240 patients with MDS studied cytogenetically at diagnosis between 1981 and 1990 were followed until death or until April 1992 to evaluate the prognostic significance of FAB classification, age and karyotype. 61 patients (25.4%) subsequently transformed into AML and 176 (73.3%) died during the follow-up period. Patien...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)00131-s
更新日期:1995-05-01 00:00:00
abstract::Imatinib mesylate (IM) is the treatment of choice in patients with newly diagnosed chronic myeloid leukemia (CML), irrespectively of their age. Nevertheless, information regarding tolerability and responses in advanced-age patients, a subgroup in which co-morbidities and other factors may influence outcome, is scarce,...
journal_title:Leukemia research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.leukres.2011.01.017
更新日期:2011-09-01 00:00:00
abstract::This study was conducted to determine the frequency of the most common fusion genes in Mexican pediatric patients with acute lymphoblastic leukemia (ALL). Molecular analysis using RT-PCR was carried out in 53-blood samples: 52 patients with de novo ALL and one with relapsed ALL. The ETV6-RUNX1 fusion was found in 7 ca...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.03.021
更新日期:2008-10-01 00:00:00
abstract::Cell line PER-423 was derived from the cells of a patient with an immature acute T-lymphoblastic leukaemia and the growth of this human cell line is strictly dependent on interleukin-2 (IL-2). PER-423 cells express the p75 (beta) subunit of the IL-2 receptor (IL-2R beta), while the p55 chain (IL-2R alpha) is not detec...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90141-7
更新日期:1993-01-01 00:00:00
abstract::Osteogenic growth peptide (OGP) is a peptide exerting regulatory effects on the bone and on bone marrow. The carboxy-terminal pentapeptide (OGP10-14) is the biologically active portion of OGP. We evaluated OGP10-14 hematopoietic activity performing colony-forming tests on human stem cells derived by bone marrow, perip...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(02)00008-5
更新日期:2002-09-01 00:00:00
abstract:PURPOSE:The study aims to develop a prognostic scoring system based on prognostic lncRNAs for acute myeloid leukemia (AML). METHODS:Based on lncRNA expression profiles downloaded from The Cancer Genome Atlas (TCGA), differentially expressed long noncoding RNAs (DELs) between good prognosis and bad prognosis samples we...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2019.106261
更新日期:2020-01-01 00:00:00
abstract::Over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), playing a role in leukemogenesis while decreased expression of PU.1 induces AML in mice model. Therefore, we speculated that there is an inverse relationship between these two factors. To clarify this, we measured the expression level of Fl...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.07.015
更新日期:2006-06-01 00:00:00
abstract::Concern has been expressed recently about apparent increases in the incidence of leukaemia amongst young people living in certain geographical areas. We analysed the incidence of childhood leukaemia in South-East Scotland (excluding North-East Fife) from 1970 to 1984. There was a significant geographical variation in ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(86)90091-3
更新日期:1986-01-01 00:00:00
abstract::Malignant plasma cells exert osteoclast-like activity in vitro. We investigated the function of the calcitonin (CT) receptor (R) on myeloma cells from patients and in myeloma cell lines. Primary myeloma cells expressed high CTR levels whereas the cell lines uniformly exposed the CTR-2 variant expressed by osteoclasts....
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.07.009
更新日期:2008-04-01 00:00:00
abstract::In a patient affected with chronic lymphocytic leukemia with lymphocyte surface mu and kappa determinants and vacuolated bone marrow plasma cells, the serum contained polymers of a truncated mu chain and normal-sized kappa chains. These light chains were present as monomers and covalent dimers in studies performed und...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90129-9
更新日期:1993-06-01 00:00:00
abstract:BACKGROUND:Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of iron overload and associated organ damage, and death. Emerging evidence indicates that iron chelation therapy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especially those classi...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2014.02.003
更新日期:2014-05-01 00:00:00
abstract::Leukemic bcr-abl positive dendritic cells (DCs) are likely to be present in vivo in chronic myelogenous leukemia (CML) patients, but no data are available on their functional qualities. We analyzed the circulating BDCA-1+ myeloid DC compartment in 15 chronic phase CML patients. Phenotypic features of CML DCs were comp...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.11.028
更新日期:2006-07-01 00:00:00
abstract::Prospective data are needed to ascertain the impact of iron chelation therapy in patients with myelodysplastic syndromes. The present 5-year prospective registry analysis was conducted to compare clinical outcomes between chelated and nonchelated patients with lower-risk myelodysplastic syndromes and transfusional iro...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2017.01.033
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivit...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2018.06.014
更新日期:2018-08-01 00:00:00
abstract::Information about the expression of some myelomonocytic markers in lymphocytes of patients with B-CLL is scarce. We studied the CD13, CD14, CD11c and CD68 surface antigens in 42 controls and in 38 patients with B-CLL to detect their possible reactivity. Eighty-nine percent of B-CLL expressed very strongly the CD14 ant...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90177-9
更新日期:1992-01-01 00:00:00
abstract::A clonal origin of hematopoiesis was studied by investigation of X-chromosome inactivation patterns (XCIP) in isolated granulocyte, CD14(+) and CD3(+) subpopulations obtained from bone marrow and peripheral blood of 36 female patients with primary myelodysplastic syndrome (MDS). Clonality was assessed by PCR amplifica...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.08.008
更新日期:2005-04-01 00:00:00
abstract::Our aim was to examine in 17 patients with MDS the effects of PMA activated and non-activated autologous lymphocytes on selected bone marrow CD34+ progenitors, in dose response studies. We used a double layer culture technique. Compared with controls, there was no difference in the colony growth promoting capacity of ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2011.03.017
更新日期:2011-09-01 00:00:00
abstract::Mantle cell lymphoma (MCL) an incurable B-cell, non-Hodgkin lymphoma (NHL) urgently requires new treatments. We assessed reovirus mediated oncolysis in a panel of human MCL cell lines. In vitro, we found the cytopathic effect of reovirus infection ranged from high to very limited and correlated with levels of Ras acti...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.05.020
更新日期:2010-01-01 00:00:00
abstract::Methods for ex vivo purging of neoplastic cells from harvested marrow are being developed to increase the efficacy of autologous transplantation. One approach is selective photosensitization, using sensitizing compounds and light radiation. Pyrene-containing fatty acids and lipids are potent photosensitizers, e.g. 12-...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90170-c
更新日期:1992-01-01 00:00:00
abstract::To determine the role of cell-mediated immunity (CMI) to cytomegalovirus (CMV) in leukemic children after CMV infection, CMI to CMV antigen was studied using CMV-specific lymphocyte blastogenic responses (LBR) and interferon (IFN) production. Four children, who continuously secreted CMV in urine more than 2 years afte...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)90086-8
更新日期:1994-07-01 00:00:00
abstract::We have studied the survival of clonogenic neoplastic cells of a murine pre-B-lymphoma (BCl-1) of the spleen in culture. We have found quantitative deficiencies such as reduced surface adherence of stromal cells and impaired CFU-F (colony forming units-fibroblast) and pre-CFU-F colony and layer formation in stromal cu...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90088-3
更新日期:1993-07-01 00:00:00
abstract::Resistance to chronic myeloid leukemia (CML) drug STI571 has been associated with point mutations in the kinase domain of BCR-ABL. For example, the mutation T315I (g. 68721C>T) and, to a lesser extent, Y253F (g. 58796A>T) appear in a significant proportion of patients resistant to treatment. Mutations appear intimatel...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(03)00066-3
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND:T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and imp...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2018.01.009
更新日期:2018-04-01 00:00:00
abstract::Aberrant expression of tumor suppressor genes WT 1, RB 1, p53, homozygous deletion of p16 gene and their relationship with expression of oncogenes BCR-ABL, TEL-AML 1, MLL-AF 4, E2A-PBX 1, SIL-TAL 1 were determined in bone marrow samples of children with de novo B-lineage (n=170) and T-lineage (n=25) acute lymphoblasti...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.04.006
更新日期:2005-11-01 00:00:00
abstract::In a previous study we reported that a new anthracycline derivative (moflomycin) exhibited a higher antileukemic activity compared to other anthracyclines, such as daunorubicin and doxorubicin. To explain the superior antileukemic effect of moflomycin and to disclose a possible structure-activity relationship, we inve...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(95)00155-7
更新日期:1996-02-01 00:00:00
abstract::This report describes a unique case of acute myeloid leukemia with hypergranular cytoplasm and t(X;11)(q24;q23). The breakpoint on 11q23 was identified within the MLL gene. The hypergranular cytoplasm of leukemic cells and the associated coagulopathy resembled a characteristic of acute promyelocytic leukemia, despite ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(98)00131-3
更新日期:1999-01-01 00:00:00
abstract::Based on Bcl-X(L) overexpression studies we identified type I and type II follicular lymphoma cell lines in response to TRAIL. We demonstrate here that either amount of caspase-8 activation or Bid cleavage could not define the dependence on mitochondria. Furthermore, an inhibitor of NF-kappaB, PDTC, enabled TRAIL to a...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.09.025
更新日期:2009-06-01 00:00:00
abstract::Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but to date no previous research has focused on the role of analgesics in the etiology of multiple myeloma (MM). We conducted a hospital-based case-control study of 117 patients with primary, incident MM and 483 age and residence mat...
journal_title:Leukemia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.leukres.2006.07.027
更新日期:2007-04-01 00:00:00
abstract::It has been suggested that acidic isoferritins play a major role in the regulation of human granulocyte-macrophage (CFU-GM) proliferation. Such regulatory isoferritins are said to occur in some human tissues including both leukaemic and normal leucocytes, and certain established cell lines. They are glycosylated and b...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(84)90065-1
更新日期:1984-01-01 00:00:00