Abstract:
:Fusion proteins encoded by several types of chromosomal translocations in promyelocytic leukemia can serve as aberrant transcriptional repressors relying on recruitment of histonedeacetylases (HDACs) into DNA-associated multi-protein complexes. Thus, inappropriate modulation of chromatin structure by HDACs and subsequently repression of gene expression that is critical for myeloid differentiation appear to be major factors in the development of the disease. They identify inhibitors of HDACs as prime candidates for novel anti leukemic drugs. Over the last years several candidate compounds have been introduced into clinical trials and have successfully been used in compassionate use protocols. Amongst them phenylbutyrate served as the first example to establish proof of principle. Novel drugs such as suberoylanilide hydroxamic acid (SAHA) are developed for example by modifications of the microbial HDAC inhibitory compound trichostatin A with a hydroxamic acid as the key structural element. The branched chain carboxylic acid valproic acid (VPA) that is in use as antiepileptic drug over decades was also discovered to inhibit HDACs and preferentially class I HDACs. HDAC inhibition is likely to mediate the teratogenic side effects of VPA but not the antiepileptic activity. In contrast to other HDAC inhibitors VPA also induces proteasomal degradation of HDAC2. None of the currently available compounds may be the optimum HDAC inhibitory drug but each of them may serve to answer urgent questions concerning the concept of HDAC inhibition in the treatment of malignant diseases. Prominent questions are i) whether and by which mechanisms HDAC inhibition can be expected to affect a malignant disease not only in the early stage but also at later stages that have acquired additional genetic defects, ii) which forms of cancer in addition to myelocytic leukemia respond to HDAC inhibition, iii) by which markers those susceptible forms could be identified and iv) which individual HDACs are the most critical isoenzymes to address in treatment of malignant diseases.
journal_name
Ann Hematoljournal_title
Annals of hematologyauthors
Göttlicher Mdoi
10.1007/s00277-004-0850-2subject
Has Abstractpub_date
2004-01-01 00:00:00pages
S91-2eissn
0939-5555issn
1432-0584journal_volume
83 Suppl 1pub_type
杂志文章,评审abstract::Information regarding prognostic determinants of outcome after splenectomy for adult immune thrombocytopenic purpura (ITP) and the management of postsplenectomy relapse is limited. Among 140 adult patients with ITP who had therapeutic splenectomy at our institution, 88% achieved either a complete (platelets > 150 x 10...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-002-0461-8
更新日期:2002-06-01 00:00:00
abstract::A case of congenital leukemia with monosomy 7 is reported. Immunological study of the blast cells using monoclonal antibodies was suggestive of both myelomegakaryocytic and T-lymphoblastic leukemia. Chromosomal analysis of the bone marrow cells showed monosomy 7. Chemotherapy was initiated with a combination of adriam...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/BF01836073
更新日期:1992-12-01 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for relapsed, advanced, and otherwise incurable non-Hodgkin's lymphomas (NHL) suggested by the existence of a graft-versus-lymphoma effect. The main complications are graft-versus-host disease and infections. We performed a retrospec...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-017-2934-9
更新日期:2017-05-01 00:00:00
abstract::Ixazomib, the first oral proteasome inhibitor (PI), has been approved for the treatment of relapsed refractory multiple myeloma (RRMM) in combination with lenalidomide and dexamethasone, based on the TOURMALINE-MM1 phase 3 trial, which demonstrated the efficacy and safety of this all-oral triplet, compared with lenali...
journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00277-020-03985-9
更新日期:2020-06-01 00:00:00
abstract::Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet ...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-005-0073-1
更新日期:2006-06-01 00:00:00
abstract::Hemoglobin (Hb) Korle-Bu (beta73; Asp-Asn) is the most frequent of the rare beta-chain variants in the population of West Africa whereas Hb E (beta26; Glu-Lys) is common among the Southeast Asian population. We report a hitherto undescribed condition in which these two beta-chain variants co-segregate. The proband was...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-002-0485-0
更新日期:2002-07-01 00:00:00
abstract::Renal failure is one of the worst complications occurring in multiple myeloma (MM) patients. It does not affect survival if reverted by a prompt chemotherapy before the damage becomes irreversible; therefore, the early diagnosis of renal dysfunction is crucial. High and low molecular weight urinary proteins have prove...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-003-0699-9
更新日期:2003-08-01 00:00:00
abstract::The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma (NKTCL) remains to be established. A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively reviewed. Among the patients with stage I-II disease, 58.3 % received radiotherapy (RT) ± chemotherapy, and 41.7 % re...
journal_title:Annals of hematology
pub_type: 临床试验,杂志文章
doi:10.1007/s00277-015-2395-y
更新日期:2015-09-01 00:00:00
abstract::Assay of phosphotyrosine levels using flow cytometry has been used to identify patients with chronic myelogenous leukemia positive for the Bcr-Abl fusion gene. We hypothesized that clinical monitoring could identify treatment response through reductions in intragranulocyte phosphotyrosine. Initially, we studied cell l...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-008-0563-z
更新日期:2009-01-01 00:00:00
abstract::This is a retrospective, multicenter study to evaluate biological features and outcome of elderly patients diagnosed with acute lymphoblastic leukemia (ALL) during the last 10 years in ten hematological centers in Poland. Eighty-seven patients aged 60 years or older were studied. To our knowledge, this is one of the l...
journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00277-003-0808-9
更新日期:2004-04-01 00:00:00
abstract::Autoantibody against erythrocytes has occasionally been observed in patients with de novo acute myelocytic leukemia (AML). However, it is not clear whether this autoantibody in AML patients induces frank hemolysis (autoimmune hemolytic anemia, AIHA), as seen in lymphoid neoplasms. We present two de novo AML patients w...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/BF00663016
更新日期:1996-01-01 00:00:00
abstract::In view of obscure clinical and biological significance of leukemic cells heterogeneity, we studied the efficacy of apoptosis, proliferation, and expression levels of the Bcl-2, MDR1, LRP, and BCRP genes in sorted CD34+ and CD34- subpopulations of childhood AML leukemic samples. In five out of nine cases, CD34+ cells ...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-008-0439-2
更新日期:2008-05-01 00:00:00
abstract::FLT3 and its ligand (FL) are one of the regulators of normal hematopoiesis. Ligand-independent activation of FLT3 occurs in about 30% of acute myeloid leukemia cases and is one goal for selectively targeted therapies. However, the function of FLT3/FL in the regulation of non-malignant immature hematopoietic cells is p...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-008-0605-6
更新日期:2009-03-01 00:00:00
abstract::Venous thromboembolism (VTE) is a well-recognized complication in pediatric oncology patients. Studies in adult oncology patients have suggested a potential negative association between VTE and survival, but this association has not been examined in pediatric patients yet. The aim of this study was to assess the assoc...
journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00277-018-3371-0
更新日期:2018-10-01 00:00:00
abstract::Sickle cell disease (SCD) is a relatively common inherited hemolytic anemia among individuals of African descent. Genetic factors might clarify clinical diversity of the disease and variations in treatment response. Some researchers investigated heme oxygenase-1 (HMOX1) or chemokine receptor 5 (CCR5Δ32) genotypes amon...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-019-03697-9
更新日期:2019-08-01 00:00:00
abstract::Recently, the combination of rituximab and bendamustine (R-Benda) has been defined as highly active in patients with follicular lymphomas, but little is known about the efficacy of R-Benda in mucosa-associated lymphoid tissue (MALT) lymphoma. In a retrospective analysis, we have defined 14 patients with MALT lymphoma ...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-013-1865-3
更新日期:2014-02-01 00:00:00
abstract::Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system (CNS). Neurological manifestations of HLH have been recognized in different studies with children, but they remain relat...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-017-3035-5
更新日期:2017-08-01 00:00:00
abstract::Neutropenic enterocolitis (NE) is a severe gastrointestinal complication in patients who undergo aggressive chemotherapy. It is a necrotizing inflammation of the cecum, colon, and the terminal part of the ileum. The serious clinical state of NE patients requires very frequent surgical consultations; however, in a few ...
journal_title:Annals of hematology
pub_type: 杂志文章,评审
doi:10.1007/s00277-003-0815-x
更新日期:2004-08-01 00:00:00
abstract::Cryoglobulinemia is uncommon in Southern Chinese in Hong Kong, with tropical climates and low incidence of hepatitis C virus (HCV) infection. Eight positive cases were detected among 481 patients screened for cryoglobulins over a 10-year period. Three HCV carriers (38%) ran benign courses. The others included two carr...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-004-0955-7
更新日期:2005-02-01 00:00:00
abstract::The production of erythropoietin (Epo), the glycoprotein hormone which controls red blood cell formation, is regulated by feedback mechanisms sensing tissue oxygenation. The mechanism of the putative oxygen sensor has yet to be elucidated. There is evidence that at least two pathways participate in hypoxia signal tran...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s002770050514
更新日期:1999-06-01 00:00:00
abstract::The impact of intraocular involvement (IOL) in primary CNS lymphoma (PCNSL) has not been sufficiently evaluated. Here, we present the analysis of IOL in the only completed randomized phase III trial in PCNSL. The G-PCNSL-SG1 study evaluated the role of whole-brain radiotherapy in primary therapy of PCNSL. Data of the ...
journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00277-014-2212-z
更新日期:2015-03-01 00:00:00
abstract::Less toxic and more active treatments are needed for indolent lymphomas as there is no curative treatment, and patients eventually die due to complications related to their disease. The purpose of the present study was to assess the antitumour activity of the combination of low doses of Enzastaurin and Lenalidomide (R...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-012-1490-6
更新日期:2012-10-01 00:00:00
abstract::Infections and especially blood stream infections (BSI) with gram-negative bacteria (GNB) represent a major threat for patients with hematological diseases undergoing chemotherapy and mainly contribute to morbidity and mortality. In this retrospective single-center study, we analyzed the impact of BSI with different g...
journal_title:Annals of hematology
pub_type: 临床试验,杂志文章
doi:10.1007/s00277-018-3423-5
更新日期:2018-11-01 00:00:00
abstract::The main purpose of this report is to focus on the importance of an accurate etiologic diagnosis of gastrointestinal complications during chemotherapy for acute myeloid leukemia, taking into account that a syndrome characterized by bowel wall thickening associated with diarrhea and abdominal pain may have etiologies d...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-003-0755-5
更新日期:2004-03-01 00:00:00
abstract::Secondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes an isolated CNS relapse or CNS involvement with systemic disease progression. This rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. However, there are limited data about i...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-010-1104-0
更新日期:2011-05-01 00:00:00
abstract::Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated ultra-rare diseases. Quality of life (QoL) evaluation tools used in studies for AA and PNH are unspecific and designed for cancer patients (e.g., the European Organization for Research and Treatment of Cancer Quality of Life Q...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-016-2867-8
更新日期:2017-02-01 00:00:00
abstract::A retrospective study of 120 patients with the clinically and histologically established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed to determine prognostic factors of predictive value, including parameters characterizing the dynamics of hematopoietic cell kinetics. In contrast to previous stud...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s002770050474
更新日期:1999-02-01 00:00:00
abstract::Recent studies have demonstrated that direct cell-to-cell interaction is one of the microenvironment factors for transdifferentiation of adult stem cells into cardiomyocytes. We investigated whether transdifferentiation of mesenchymal stem cells (MSCs) into cardiomyocytes was dependent on developmental stages of cocul...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-005-1068-7
更新日期:2005-10-01 00:00:00
abstract::Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials and collected and treated consecutively by the Lazio Coopera...
journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00277-016-2884-7
更新日期:2017-03-01 00:00:00
abstract::Early mortality remains a major challenge for the treatment of hemophagocytic lymphohistiocytosis (HLH), which warrants the need for prompt risk stratification in the early phase of the disease. We retrospectively analyzed clinical features of a cohort of pediatric patients managed at a tertiary hospital in southern C...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-016-2727-6
更新日期:2016-09-01 00:00:00