Abstract：
:Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000× 10(9)/L. Up to week 24, 8 of 26 evaluable patients (31%) achieved a ≥35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a ≥50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT00745550.
journal_name
Bloodjournal_title
Bloodauthors
Komrokji RS,Seymour JF,Roberts AW,Wadleigh M,To LB,Scherber R,Turba E,Dorr A,Zhu J,Wang L,Granston T,Campbell MS,Mesa RAdoi
10.1182/blood-2013-02-484832subject
Has Abstractpub_date
2015-04-23 00:00:00pages
2649-55issue
17eissn
0006-4971issn
1528-0020pii
blood-2013-02-484832journal_volume
125pub_type
杂志文章,多中心研究相关文献
BLOOD文献大全abstract：:We used a sensitive, quantitative bisulfite PCR assay, methylation sensitive single nucleotide primer extension (Ms-SNuPE), to measure methylation of the 5' CpG islands of c-abl and p15 in chronic myelogenous leukemia (CML) patients during progression. We found that the Pa promoter of c-abl was methylated in 81% (17/2...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：:Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. However, only a limited number of target genes have been identified. We have studied 10 MCL cell lines and 28 primary tumors with a combination of a high-density single...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-07-170183
更新日期：2009-03-26 00:00:00
abstract：:The myeloid cell-surface glycoprotein CD13/aminopeptidase N (APN; EC 3.4.11.2) contains a pentapeptide (HExxH) in its extracellular domain that is characteristic of many zinc-dependent metalloproteinases. This region contains residues important for zinc binding and constitutes part of the catalytic domain of several m...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-06-15 00:00:00
abstract：:Multiple myeloma (MM) is one of the most common hematologic malignancies. Despite extensive therapeutical approaches, cures remain rare exceptions. An important issue for future immunologic treatments is the characterization of appropriate tumor-associated antigens. Recently, a highly glycosylated mucin MUC1 was detec...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2004-01-0366
更新日期：2005-03-01 00:00:00
abstract：:Complement plays a key role in host defense, but its dysregulation can cause autologous tissue injury. Complement activation is normally controlled by regulatory proteins, including factor H (FH) in plasma and membrane cofactor protein (MCP) on the cell surface. Mutations in FH and MCP are linked to atypical hemolytic...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2016-07-728253
更新日期：2017-03-02 00:00:00
abstract：:We have shown that cytosol samples from human leukemia cells frequently contain glucocorticoid receptor fragments that have a mol wt (Mr) of approximately 52,000. In the present study we demonstrate that the Mr approximately 52,000-receptor fragments are derived from intact glucocorticoid receptors (Mr approximately 9...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:We describe the membrane localization of a new platelet-specific alloantigen, designated Naka, that is involved in refractoriness to HLA-matched platelet transfusions. By indirect immunoprecipitation, anti-Naka antibody precipitated a single, radiolabeled platelet membrane protein with a molecular weight (mol wt) of 9...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:Homeostatic mechanism by which peripheral T-cell subsets are maintained in vivo remains largely unknown. Using a T-cell proliferation model under lymphopenic settings, we now demonstrate that gammadelta T cells limit CD8 T-cell expansion but not the initial proliferation after transfer into lymphopenic recipients. Int...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-12-192997
更新日期：2009-06-18 00:00:00
abstract：:Recombinant (r) and natural human (h) macrophage colony-stimulating factor (M-CSF, CSF-1) have been considered poor stimulators of macrophage progenitor cells present in human marrow, although they are potent stimulators of these cells in mouse marrow. We compared the growth characteristics of rhM-CSF-responsive human...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1990-07-15 00:00:00
abstract：:Interleukin-3 (IL-3) regulates growth and differentiation of multipotential as well as lineage-committed progenitor cells. The human IL-3 receptor (IL-3R) consists of the alpha and common beta (beta c) subunits. The alpha subunit (IL-3R alpha) is specific for IL-3 and binds IL-3 with low affinity. In contrast, the bet...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:The malaria parasite Plasmodium falciparum releases the ring-infected erythrocyte surface antigen (RESA) inside the red cell on entry. The protein migrates to the host cell membrane, where it binds to spectrin, but neither the nature of the interaction nor its functional consequences have previously been defined. Here...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2007-02-076919
更新日期：2007-08-01 00:00:00
abstract：:Purified human lactoferrin was assessed for its influence in vivo in untreated mice and in mice undergoing rebound myelopoiesis after sublethal dosages of Cytoxan. Fully iron-saturated lactoferrin suppressed the numbers of granulocytes and monocytes per femur, the numbers of granulocyte-macrophage progenitor cells (CF...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:Drug-dependent antibodies (DDAbs) can cause the precipitous destruction of platelets if a patient is exposed to the drug for which the antibodies are specific. The molecular character of the epitopes recognized is poorly understood, and the mechanism by which drugs promote tight binding of these antibodies to platelet...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2002-07-2336
更新日期：2003-02-01 00:00:00
abstract：:Thrombocytopenia developed in some individuals treated with a recombinant thrombopoietin (TPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Three of the subjects who developed severe thrombocytopenia were analyzed in detail to determine the cause of their thrombocytopenia. Ex...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.v98.12.3241
更新日期：2001-12-01 00:00:00
abstract：:Binding of platelets to fibrinogen via integrin alphaIIbbeta3 stimulates cytoskeletal reorganization and spreading. These responses depend on tyrosine phosphorylation of multiple proteins by Src family members and Syk. Among Src substrates in platelets is adhesion- and degranulation-promoting adapter protein (ADAP), a...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2009-08-238238
更新日期：2010-03-18 00:00:00
abstract：:Although well characterized in the mouse, the role of Notch signaling in the human T-cell receptor alphabeta (TCR-alphabeta) versus TCR-gammadelta lineage decision is still unclear. Although it is clear in the mouse that TCR-gammadelta development is less Notch dependent compared with TCR-alphabeta differentiation, re...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-06-164871
更新日期：2009-03-26 00:00:00
abstract：:Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic r...
journal_title：Blood
pub_type： 杂志文章,评审
doi：10.1182/blood-2015-01-544676
更新日期：2015-06-18 00:00:00
abstract：:Active immunization with the idiotype of follicular lymphoma induces tumor-specific immunity. T cells induced in vivo by idiotype vaccination recognize human leukocyte antigen (HLA)--restricted hypervariable but not conserved idiotype peptides. We hypothesized that idiotype-directed T-cell immunity occurs naturally an...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2010-02-270199
更新日期：2010-09-09 00:00:00
abstract：:The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often tot...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1976-12-01 00:00:00
abstract：:Parasitic worms of the genus Schistosoma excrete relatively large amounts of immunogenic glycoproteins (circulating cathodic antigen [CCA]) that contain polysaccharide side chains with the trisaccharide Lewis-x (L(ex)) as a repeating unit. These carbohydrates evoke high titers of specific IgM antibodies that cross-rea...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltran...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:Stem cell factor (SCF) and interleukin-3 (IL-3) both act on several target hematopoietic populations, including mast cells. We have isolated a unique murine mast cell line, B6M, that is phenotypically similar to immature mast cells. For B6M cells, IL-3 is a survival factor and alone does not stimulate proliferation. S...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:The intestinal microbiota in allogeneic bone marrow transplant (allo-BMT) recipients modulates graft-versus-host disease (GVHD), a systemic inflammatory state initiated by donor T cells that leads to colitis, a key determinant of GVHD severity. Indole or indole derivatives produced by tryptophan metabolism in the inte...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2018-03-838193
更新日期：2018-12-06 00:00:00
abstract：:Murine myeloid cells can be transformed in vitro by infection with recombinant retroviruses carrying activated myb genes. While these myb-transformed hematopoietic cells (MTHCs) can proliferate continuously in culture, they exhibit several characteristics of progenitor cells of the granulocyte-macrophage (GM) lineage,...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Hypoxia is a strong stimulus for the transcription of a set of genes, including erythropoietin and vascular endothelial growth factor. Here we report on the cloning, functional significance, and expression of a complementary DNA (cDNA) that is involved in hypoxia-mediated expression of these 2 genes. The full-length c...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-07-15 00:00:00
abstract：:Three recipients of HLA-identical bone marrow transplants developed chronic graft-versus-host disease (cGVHD) and hypergammaglobulinemia. All three had evidence of abnormal B-lymphocyte function, including a polyclonal increase in immunoglobulins (Ig), antinuclear antibodies, rheumatoid factor, lymphocytotoxins, and i...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1981-10-01 00:00:00
abstract：:Dentin matrix protein 1 (DMP1) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a group of proteins initially described as mineralized extracellular matrices components. More recently, SIBLINGs have been implicated in several key steps of cancer progression, including angiogenes...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2010-08-298810
更新日期：2011-02-24 00:00:00
abstract：:Development of acute graft-versus-host disease (aGVHD) predisposes to chronic GVHD with autoimmune manifestations. A characteristic of experimental aGVHD is the de novo generation of autoreactive T cells. Central tolerance is dependent on the intrathymic expression of tissue-restricted peripheral self-antigens (TRA), ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2012-12-474759
更新日期：2013-08-01 00:00:00
abstract：:Malignant cells are capable of influencing the microenvironment in a manner that facilitates tumor cell survival. Bidirectional crosstalk between chronic lymphocytic leukemic (CLL) cells and marrow-derived mesenchymal stromal cells (MSCs) activates both cell types. In this study, we observed that the conditioned mediu...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2010-02-269894
更新日期：2010-10-21 00:00:00
abstract：:The pp65(495-503) cytotoxic T-lymphocyte (CTL) epitope from cytomegalovirus (CMV) is universally recognized among CMV+ individuals who express an allele of the human leukocyte antigen A (HLA-A*0201). The relative binding affinity of the epitope to HLA-A*0201 is moderate, and its increased activity might prove benefici...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.v97.6.1776
更新日期：2001-03-15 00:00:00
