Abstract:
:Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph(+)) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasa-tinib (a dual-specific SRC/BCR-ABL kinase inhibitor) were compared in a preclinical mouse model of intracranial Ph(+) leukemia. Clinical dasatinib treatment in patients with CNS Ph(+) leukemia was assessed. In preclinical studies, dasatinib increased survival, whereas imatinib failed to inhibit intracranial tumor growth. Stabilization and regression of CNS disease were achieved with continued dasa-tinib administration. The drug also demonstrated substantial activity in 11 adult and pediatric patients with CNS Ph(+) leukemia. Eleven evaluable patients had clinically significant, long-lasting responses, which were complete in 7 patients. In 3 additional patients, isolated CNS relapse occurred during dasatinib therapy; and in 2 of them, it was caused by expansion of a BCR-ABL-mutated dasatinib-resistant clone, implying selection pressure exerted by the compound in the CNS. Dasatinib has promising therapeutic potential in managing intracranial leukemic disease and substantial clinical activity in patients who experience CNS relapse while on imatinib therapy. This study is registered at ClinicalTrials.gov as CA180006 (#NCT00108719) and CA180015 (#NCT00110097).
journal_name
Bloodjournal_title
Bloodauthors
Porkka K,Koskenvesa P,Lundán T,Rimpiläinen J,Mustjoki S,Smykla R,Wild R,Luo R,Arnan M,Brethon B,Eccersley L,Hjorth-Hansen H,Höglund M,Klamova H,Knutsen H,Parikh S,Raffoux E,Gruber F,Brito-Babapulle F,Dombret H,Duadoi
10.1182/blood-2008-02-140665subject
Has Abstractpub_date
2008-08-15 00:00:00pages
1005-12issue
4eissn
0006-4971issn
1528-0020pii
blood-2008-02-140665journal_volume
112pub_type
临床试验,杂志文章相关文献
BLOOD文献大全abstract::The primary objective was to describe the prevalence and characteristics of microbiologically defined infections and infection-related mortality (IRM) in 492 children with acute myeloid leukemia enrolled on CCG 2961. Secondary objectives were to determine the relationship between demographic, disease-related, and ther...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2007-05-091942
更新日期:2007-11-15 00:00:00
abstract::Silent cerebral infarct (SCI) is the most common form of neurologic disease in children with sickle cell anemia (SCA). SCI is defined as abnormal magnetic resonance imaging (MRI) of the brain in the setting of a normal neurologic examination without a history or physical findings associated with an overt stroke. SCI o...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2011-02-272682
更新日期:2012-05-17 00:00:00
abstract::Heavy chain ferritin (H-ferritin) is a component of the iron-binding protein, ferritin. We have previously shown that H-ferritin inhibits anti-CD3-stimulated lymphocyte proliferation and that this was due to increased production of interleukin-10 (IL-10). In the present study we have shown that induction of IL-10 prod...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.9.3326
更新日期:2002-05-01 00:00:00
abstract::The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-11-467191
更新日期:2013-07-18 00:00:00
abstract:UNLABELLED:Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-n...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-09-456566
更新日期:2013-01-31 00:00:00
abstract::Through the procedure of gene amplification combined with hybridization to synthetic 19 base pair (bp) oligonucleotide probes, it has been possible to identify nine different mutations in the DNA of 47 subjects from Turkey and Northern Cyprus with a beta-thalassemia homozygosity. The IVS-I nucleotide (nt) 110 G----A a...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease defined by transcriptional classifications, specific signaling and survival pathways, and multiple low-frequency genetic alterations. Preclinical model systems that capture the genetic and functional heterogeneity of DLBCL are urgently needed. Here, we g...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-09-672352
更新日期:2016-05-05 00:00:00
abstract::At inflammatory sites, proteoglycans are both secreted by activated mononuclear leukocytes and released as a consequence of extracellular matrix degradation. Chondroitin 4-sulfate proteoglycans constitute the predominant ones produced by activated human monocytes/macrophages. In this study, we show that two chondroiti...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-02-15 00:00:00
abstract::Transcriptional profiles of cultured primary human erythroid cells were examined to identify those genes involved in the control of erythroid growth during the terminal phase of maturation. Our in silico screening strategy indicated that a hypoxia-inducible proapoptotic member of the Bcl-2 gene family called Nix is ex...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-11-3324
更新日期:2003-07-15 00:00:00
abstract::A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::A primary function of the World Marrow Donor Association is to establish general guidelines covering collaboration between international donor registries and practice in regard to bone marrow transplants (BMTs) in which the donor and recipient reside in different countries. To this end, a special report proposing spec...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Phospholipase A(2) type IVA (IVAPLA(2)) is a cytosolic enzyme that on activation selectively releases arachidonic acid (AA) from cell membrane phospholipids. Both AA and lysophospholipid, products of the enzymic reaction, can function as signal transducers in cellular interactions. The enzyme is present in most cells,...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-09-2698
更新日期:2004-05-01 00:00:00
abstract::Bortezomib (PS-341), a selective inhibitor of proteasomes, induces apoptosis in multiple myeloma (MM) cells; however, prolonged drug exposure may result in cumulative toxicity and the development of chemoresistance. Here we show that combining PK-11195 (PK), an antagonist to mitochondrial peripheral benzodiazepine rec...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-02-0547
更新日期:2004-10-15 00:00:00
abstract::Dendritic cells (DCs) represent a family of ontogenically distinct leukocytes involved in immune response regulation. The ability of DCs to stimulate T-cell immunity has led to their use as vectors for immunotherapy vaccines. However, it is unclear whether and to what degree in vitro-generated DCs are representative o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract::Adult T-cell leukemia (ATL) is neoplasm of the mature helper T lymphocytes and human T-cell lymphotropic virus type-I (HTLV-I) has been shown to be causative virus of ATL. Because HTLV-I integrates its provirus randomly into host chromosomal DNA, monoclonal integration of HTLV-I provirus indicates the clonal prolifera...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::A critical role for the endothelium of yolk sac and dorsal aorta has been shown in embryonic hematopoiesis. A stromal cell line derived from yolk sac, YSCL-72, has been chosen to search for a novel molecule associated with embryonic hematopoiesis. Analysis between YSCL-72 and an adult aorta-derived endothelial cell li...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.7.2134
更新日期:2001-10-01 00:00:00
abstract::Oxidative stress has been implicated in the triggering of apoptosis in neutrophils. Because red blood cells (RBCs) are well known to scavenge oxidants including H2O2, we tested the hypothesis that RBCs inhibit apoptosis of neutrophils by reducing intracellular oxidative stress. Apoptosis of neutrophils was evaluated b...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-06-01 00:00:00
abstract::A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::Melanotransferrin (MTf) or tumor antigen p97 is a transferrin homolog that binds one iron (Fe) atom and has been suggested to play roles in a variety of processes, including Fe metabolism, eosinophil differentiation, and plasminogen activation. Considering the vital role of Fe in many metabolic pathways, such as DNA a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4174
更新日期:2006-04-01 00:00:00
abstract::Mammalian 15-lipoxygenases, which have been implicated in the differentiation of hematopoietic cells are commonly regarded as cytosolic enzymes. Studying the interaction of the purified rabbit reticulocyte 15-lipoxygenase with various types of biomembranes, we found that the enzyme binds to biomembranes when calcium i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Interleukin 21 (IL-21) is a member of the common gamma-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we ge...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-021600
更新日期:2007-03-01 00:00:00
abstract::Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of p...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::Cancer patients are at increased risk of deep vein thrombosis and pulmonary embolism. The incidence among different groups of cancer patients varies considerably depending on clinical factors, the most important being tumor entity and stage. Biomarkers have been specifically investigated for their capacity of predicti...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2013-04-460147
更新日期:2013-09-19 00:00:00
abstract::Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-01-15 00:00:00
abstract::We have previously reported on a unique patient in whom homozygosity for a mutation at IRF8 (IRF8(K108E)) causes a severe immunodeficiency. Laboratory evaluation revealed a highly unusual myeloid compartment, remarkable for the complete absence of CD141 and CD161 monocytes, absence of CD11c1 conventional dendritic cel...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-04-570879
更新日期:2014-09-18 00:00:00
abstract::Mutations within exon 3 of the beta-globin gene are relatively uncommon, and many of these mutations produce a dominant thalassemia-like phenotype. We describe a novel thalassemic hemoglobinopathy caused by a single nucleotide substitution (CTG-->CCG) at codon 114 resulting in a leucine to proline substitution and des...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-02-15 00:00:00
abstract::A20 is a stress response gene in endothelial cells (ECs). A20 serves a dual cytoprotective function, protecting from tumor necrosis factor (TNF)-mediated apoptosis and inhibiting inflammation via blockade of the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we evaluated the molecular basis of ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-02-0635
更新日期:2004-10-15 00:00:00
abstract::Mice homozygous for Hertwig's anemia, an/an, have a mild macrocytic anemia and are refractory to the potentially curative action of exogenously administered erythropoietin (EP). Both red and white blood cell numbers are decreased. One possible explanation is that a precursor stem cell population is in short supply. We...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract::Erdheim-Chester disease (ECD) pathophysiology remains largely unknown. Its treatment is not codified and usually disappointing. Interferon (IFN)-α therapy lacks efficacy for some life-threatening manifestations and has a poor tolerance profile. Because interleukin (IL)-1Ra synthesis is naturally induced after stimulat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-279240
更新日期:2010-11-18 00:00:00