Abstract:
:Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors. Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and tyrosine kinase inhibitor failure. Patients received subcutaneous omacetaxine 1.25 mg/m(2) twice daily, days 1-14, every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n = 62) received a median of 7 (range, 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit, 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% lower confidence limit, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation. This study is registered at www.clinicaltrials.gov as NCT00375219.
journal_name
Bloodjournal_title
Bloodauthors
Cortes J,Lipton JH,Rea D,Digumarti R,Chuah C,Nanda N,Benichou AC,Craig AR,Michallet M,Nicolini FE,Kantarjian H,Omacetaxine 202 Study Group.doi
10.1182/blood-2012-03-415307subject
Has Abstractpub_date
2012-09-27 00:00:00pages
2573-80issue
13eissn
0006-4971issn
1528-0020pii
blood-2012-03-415307journal_volume
120pub_type
杂志文章,多中心研究相关文献
BLOOD文献大全abstract::Global gene expression profiling of highly purified 5q-deleted CD34+CD38(-)Thy1+ cells in 5q- myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38(-)Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cel...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-03-079368
更新日期:2007-10-15 00:00:00
abstract::This study reports a lentiviral gene transfer protocol for efficient transduction of adult human peripheral blood (PB)-derived CD34+ NOD/SCID-repopulating cells (SRCs) using vesicular stomatitis virus-G protein (VSV-G)-pseudotyped lentiviruses encoding for enhanced green fluorescence protein (eGFP). Lentiviral stocks ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.2.709
更新日期:2002-01-15 00:00:00
abstract::Pediatric arterial ischemic stroke (AIS) is increasingly diagnosed and carries significant risks of recurrence, morbidity, and mortality. Anticoagulant therapy (ACT) is commonly prescribed in childhood AIS. Hemorrhagic complication rates in pediatric stroke are unknown, and adult safety data are of limited applicabili...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-06-361535
更新日期:2012-01-26 00:00:00
abstract::The mechanism of platelet release has been studied in mouse bone marrow, using scanning and transmission electron microscopy. Cytoplasmic processes extended into sinusoids by megakaryocytes were found to undergo attenuation, and at the distal end develop constrictions between segments of platelet size. Rupture at site...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 p...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1999-08-15 00:00:00
abstract::Classical hairy cell leukemia (cHCL) is characterized by a near 100% frequency of the BRAFV600E mutation, whereas ∼30% of variant HCLs (vHCLs) have MAP2K1 mutations. However, recurrent genetic alterations cooperating with BRAFV600E or MAP2K1 mutations in HCL, as well as those in MAP2K1 wild-type vHCL, are not well def...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-01-765107
更新日期:2017-10-05 00:00:00
abstract::Cells derived from human cord blood were recently used instead of bone marrow (BM) for transplantation. However, several questions concerning the potential of these cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce a graft-versus-host disease (GVHD) remain unanswered. Here w...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Vascular bypass procedures in the central nervous system (CNS) remain technically challenging, hindered by complications and often failing to prevent adverse outcome such as stroke. Thus, there is an unmet clinical need for a safe and effective CNS revascularization. Vascular endothelial growth factors (VEGFs) are pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-07-441527
更新日期:2013-08-01 00:00:00
abstract::The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hep...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-10-01 00:00:00
abstract::To characterize and clarify the function of CD34 antigen experimentally, we isolated two types of CD34 mRNA from a cDNA library of murine stromal cell line, PA-6 stimulated with lipopolysaccharide (LPS) and 12-o-tetra-decanoylphorbol 13-acetate (TPA) using a human CD34 probe. In addition to the clone (open reading fra...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Antiphospholipid syndrome is characterized by thrombosis and/or recurrent pregnancy loss in the presence of antiphospholipid antibodies (APLAs). The majority of APLAs are directed against phospholipid-binding proteins, particularly β₂-glycoprotein I (β₂GPI). Anti-β₂GPI antibodies activate endothelial cells in a β₂GPI-...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-10-313072
更新日期:2011-06-09 00:00:00
abstract::The molecular mechanisms that underlie T-cell quiescence are poorly understood. In the present study, we report a primary immunodeficiency phenotype associated with MST1 deficiency and primarily characterized by a progressive loss of naive T cells. The in vivo consequences include recurrent bacterial and viral infecti...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-378364
更新日期:2012-04-12 00:00:00
abstract::In this issue of Blood, Allinne et al propose the nucleolin-dependent activation of the translocated CCND1 allele in mantle cell lymphoma (MCL) because of its relocalization to a transcriptionally favorable area in the perinucleolar region. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2014-02-553057
更新日期:2014-03-27 00:00:00
abstract::Activation of endothelial cells, important in processes such as angiogenesis, is regulated by cell surface receptors, including those in the tyrosine kinase (RTK) family. Receptor activity, in turn, can be modulated by phosphorylation, turnover, or proteolytic release of a soluble extracellular domain. Previously, we ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-03-15 00:00:00
abstract::The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds compl...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-09-244285
更新日期:2010-03-18 00:00:00
abstract::Proinflammatory cytokines such as TNFα are elevated in patients with myeloproliferative neoplasms (MPN), but their contribution to disease pathogenesis is unknown. Here we reveal a central role for TNFα in promoting clonal dominance of JAK2(V617F) expressing cells in MPN. We show that JAK2(V617F) kinase regulates TNFα...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-348144
更新日期:2011-12-08 00:00:00
abstract::Interferon (IFN) therapy has become widely used for the treatment of chronic myelogenous leukemia. Hematologic remissions can be induced in about 60% of patients. Moreover, in a small number of patients loss of the Philadelphia (Ph) chromosome and of the BCR-ABL rearrangement is observed. We have used genomic Southern...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::The present studies investigated the effects of the recently cloned flt3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL alone was a weak growth stimulator of CD34+ BM cells, but synergistically and directly enhanced colony ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-02-15 00:00:00
abstract::A number of studies have recently demonstrated that super-enhancers, which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. Super-enhancers ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-06-792184
更新日期:2017-11-23 00:00:00
abstract::Lymphomas were studied in kindreds with autoimmune lymphoproliferative syndrome (ALPS; Canale-Smith syndrome), a disorder of lymphocyte homeostasis usually associated with germline Fas mutations. Fas (CD95/APO-1) is a cell surface receptor that initiates programmed cell death, or apoptosis, of activated lymphocytes. L...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.1.194
更新日期:2001-07-01 00:00:00
abstract::Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children wi...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:2000-03-01 00:00:00
abstract::We have demonstrated that high molecular weight kininogen (HK) binds specifically on endothelial cells to domain 2/3 of the urokinase receptor (uPAR). Inhibition by vitronectin suggests that kallikrein-cleaved HK (HKa) is antiadhesive. Plasma kallikrein bound to HK cleaves prourokinase to urokinase, initiating cell-as...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-01-15 00:00:00
abstract::The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-10-15 00:00:00
abstract::Stem cell homing into the bone microenvironment is the first step in the initiation of marrow-derived blood cells. It is reported that human severe combined immunodeficient (SCID) repopulating cells home and accumulate rapidly, within a few hours, in the bone marrow and spleen of immunodeficient mice previously condit...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.10.3283
更新日期:2001-05-15 00:00:00
abstract::Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the rem...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-07-661835
更新日期:2016-01-21 00:00:00
abstract::Adenosine diphosphate (ADP)-ribosyl-transferases (ARTs) transfer ADP-ribose from nicotinamide adenine dinucleotide (NAD) onto target proteins. T cells express ART2.2, a toxin-related, glycosylphosphatidylinositol (GPI)-anchored ecto-enzyme. After the release of NAD from cells, ART2.2 ADP-ribosylates the P2X7 purinocep...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-08-3325
更新日期:2005-05-01 00:00:00
abstract::Heme biosynthesis was examined in erythroid tissue of a 4-yr-old girl with severe sideroblastic anemia since infancy, as documented by the presence of intramitochondrial deposits of iron in erythroblasts. Free red cell protoporphyrin, urinary porphyrins, and activities of erythrocyte porphobilinogen synthase, uroporph...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::Spectrin Jendouba (alpha II/31) was found in a Tunisian family. In the heterozygous state, it is associated with asymptomatic elliptocytosis and a minimal defect in spectrin dimer self-association. On partial digestion of spectrin with trypsin, an abnormal cleavage appeared following Lys 788. Peptide and DNA sequencin...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available ...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2009-08-236356
更新日期:2010-04-08 00:00:00
abstract::The status of the T cell receptor beta and gamma genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T alpha and complete T beta gene transcripts were not detected, but a 1.0-kilobase T beta gene tran...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00