Abstract:
:Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transformed FL case and expanded findings to a combined total of 114 FLs. We report recurrent mutations in the transcription factor STAT6 in 11% of FLs and identified the STAT6 amino acid residue 419 as a novel STAT6 mutation hotspot (p.419D/G, p.419D/A, and p.419D/H). FL-associated STAT6 mutations were activating, as evidenced by increased transactivation in HEK293T cell-based transfection/luciferase reporter assays, heightened interleukin-4 (IL-4) -induced activation of target genes in stable STAT6 transfected lymphoma cell lines, and elevated baseline expression levels of STAT6 target genes in primary FL B cells harboring mutant STAT6. Mechanistically, FL-associated STAT6 mutations facilitated nuclear residency of STAT6, independent of IL-4-induced STAT6-Y641 phosphorylation. Structural modeling of STAT6 based on the structure of the STAT1-DNA complex revealed that most FL-associated STAT6 mutants locate to the STAT6-DNA interface, potentially facilitating heightened interactions. The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis.
journal_name
Bloodjournal_title
Bloodauthors
Yildiz M,Li H,Bernard D,Amin NA,Ouillette P,Jones S,Saiya-Cork K,Parkin B,Jacobi K,Shedden K,Wang S,Chang AE,Kaminski MS,Malek SNdoi
10.1182/blood-2014-06-582650subject
Has Abstractpub_date
2015-01-22 00:00:00pages
668-79issue
4eissn
0006-4971issn
1528-0020pii
blood-2014-06-582650journal_volume
125pub_type
杂志文章相关文献
BLOOD文献大全abstract::Human B-cell lines were derived by limiting dilutions of Epstein-Barr virus (EBV) transformed peripheral B cells from a patient with an autoantibody against glycoprotein (GP)Ia/IIa, and manifesting defective collagen-induced platelet aggregation and a bleeding problem. Antibody-producing clones were selected for their...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-09-15 00:00:00
abstract::Colony forming cells (CFC) with high proliferative potential have been detected in nutrient agar cultures of human bone marrow cells containing recombinant human interleukin-3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF). These CFC were detected by the formation of large colonies with diameters...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::Recent studies in humans have highlighted the importance of a distinct cellular entity, the plasmacytoid dendritic cell (PDC). To identify genes for which expression is restricted to human PDCs, a cDNA subtraction technique was applied using cDNA from activated monocyte-derived DCs (MDDCs) as competitor. In the 650 se...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-02-0638
更新日期:2002-11-01 00:00:00
abstract::It has recently been shown that the Naka antigen, which is absent in 3% to 11% of Japanese blood donors, is expressed on platelet glycoprotein IV (GPIV; CD36) (Tomiyama et al, BLOOD, 75:684, 1990). In the present studies, flow cytometry was used to distinguish differences in the reactivity of Naka+ and Naka- platelets...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::Variations within proteasome β (PSMB) genes, which encode the β subunits of the 20S proteasome, may affect proteasome function, assembly, and/or binding of proteasome inhibitors. To investigate the potential association between PSMB gene variants and treatment-emergent resistance to bortezomib and/or long-term outcome...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2012-05-426924
更新日期:2012-11-29 00:00:00
abstract::The regulator of G-protein signaling (RGS) negatively regulates the alpha subunit of G proteins by accelerating their intrinsic guanosine triphosphatase (GTPase) activity. Here are reported the isolation and characterization of a novel mouse RGS, termed RGS18, which is a new member of RGS subfamily B. Northern blot an...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.10.3051
更新日期:2001-05-15 00:00:00
abstract::Cutaneous involvement is seen in ~ 50% of adult T-cell leukemia/lymphoma (ATLL) patients. We investigated the association between skin eruption type and prognosis in 119 ATLL patients. ATLL eruptions were categorized into patch (6.7%), plaque (26.9%), multipapular (19.3%), nodulotumoral (38.7%), erythrodermic (4.2%), ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-316794
更新日期:2011-04-14 00:00:00
abstract::Ristocetin and vancomycin are structurally similar glycopeptide antibiotics. Both vancomycin and ristocetin in high concentrations (3.0 mg/ml) cause the precipitation of fibrinogen, plasminogen, and IgG from platelet-poor plasma (PPP). In contrast to ristocetin, vanomycin (0.5-1.5 mg/ml) does not agglutinate platelets...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regenera...
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:1992-11-01 00:00:00
abstract::Patients referred to tertiary care centers occasionally may have their diagnostic procedures repeated and have a final diagnosis that differs from that of the referring center. The aim of this study was to evaluate discordance rates and their clinical implications in the diagnosis of patients with myelodysplastic synd...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-342642
更新日期:2011-10-27 00:00:00
abstract::Recent findings that hemoglobin S gelation and sickling are pH-dependent and also influence oxygen affinity suggested that the red cells containing this hemoglobin variant might show an abnormal Bohr effect. We therefore studied the effects of pH variation on the in vitro oxygen affinity of whole blood from persons wi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosinophilia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that res...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-08-172767
更新日期:2009-04-09 00:00:00
abstract::Non-Hodgkin lymphomas (NHLs) are the most common cancer to affect pet dogs. In contrast to the many genes whose mutation contributes to lymphomagenesis in humans, relatively little is known about the acquired genetic alterations that lead to canine B-cell lymphomas (cBCLs). We performed a survey of 84 canine NHL tumor...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-10-602714
更新日期:2015-02-05 00:00:00
abstract::Biosynthesis of leukotrienes (LTs) occurs in human myeloid cells and B lymphocytes. However, the function of leukotrienes in B lymphocytes is unclear. Here, we report that B-cell chronic lymphocytic leukemia (B-CLL) cells produce leukotriene B(4), and that specific leukotriene biosynthesis inhibitors counteracted CD40...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-07-2546
更新日期:2005-02-01 00:00:00
abstract::Nucleophosmin-mutated acute myeloid leukemia (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Because miR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs co...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-10-532374
更新日期:2014-04-10 00:00:00
abstract::Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population that shares certain characteristics including an aberrant myeloid phenotype and the ability to suppress T cells. MDSCs have been predominantly studied in malignant diseases and findings suggest involvement in tumor-associated immune suppress...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2013-12-546416
更新日期:2014-07-31 00:00:00
abstract::The transcription factor encoded by the mi locus (MITF) is a transcription factor of the basic-helix-loop-helix zipper protein family. Mice of mi/mi genotype express a normal amount of abnormal MITF, whereas mice of tg/tg genotype do not express any MITFs due to the transgene insertional mutation. The effect of normal...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.3.645
更新日期:2001-02-01 00:00:00
abstract::Large granular lymphocytes (LGL) are defined as nonadherent mononuclear cells with cytoplasmic azurophilic granules, avid receptors for the Fc portion of IgG, and cytotoxic functions (NK or ADCC activities). In the present study, the granules of LGL isolated from human peripheral blood have been analyzed by enzyme cyt...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy h...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-03-344051
更新日期:2011-10-20 00:00:00
abstract::Krüppel-like factor 5 (Klf5) encodes a zinc-finger transcription factor and has been reported to be a direct target of C/EBPα, a master transcription factor critical for formation of granulocyte-macrophage progenitors (GMP) and leukemic GMP. Using an in vivo hematopoietic-specific gene ablation model, we demonstrate t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-12-684514
更新日期:2016-07-07 00:00:00
abstract::Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-06-226415
更新日期:2009-11-05 00:00:00
abstract::The microsomal fraction of M1 cells (an established cell line of myeloid leukemia) was capable of catalyzing acylation of sn-glycerol 3-phosphate by long-chain fatty acyl-CoA thioesters. The principal lipid product formed was identified as phosphatidic acid. Palmityl-CoA, stearyl-CoA, and oleyl-CoA were more effective...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-03-01 00:00:00
abstract::CXCR4 chemokine receptors retain hematopoietic progenitors and leukemia cells within the marrow microenvironment. We prospectively evaluated the prognostic implication of CXCR4 in 90 consecutive patients with acute myelogenous leukemia (AML) by flow cytometry. Patients were divided into groups with low (n=32), interme...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-024844
更新日期:2007-01-15 00:00:00
abstract::The clinical, morphological, immunologic, and cytogenetic features of seven cases of chronic granulated T cell lymphocytosis with neutropenia were studied. The disorder was characterized by moderate blood and bone marrow lymphocytosis, neutropenia, polyclonal hypergammaglobulinemia, splenomegaly, absence of lymphadeno...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and adenosine triphosphate s...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-03-492504
更新日期:2013-08-08 00:00:00
abstract::A new type of A alpha Glu-11 to Gly substitution has been identified in a congenitally abnormal fibrinogen, fibrinogen Mitaka II, derived from a 14-year-old female suffering from easy bruising since childhood. Plasma of the patient and fibrinogen purified therefrom were found to clot slowly by thrombin but in a normal...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is a severe renal disease that is associated with defective complement regulation caused by multiple factors. We previously described the deficiency of factor H-related proteins CFHR1 and CFHR3 as predisposing factor for aHUS. Here we identify in an extended cohort of 147 aHUS...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-109876
更新日期:2008-02-01 00:00:00
abstract::The replating capability of human umbilical cord blood (CB) multipotential (CFU-GEMM) progenitors was assessed in vitro as an estimate of self-renewal using erythropoietin (Epo), steel factor (SLF), and either fetal bovine serum (FBS) or CB plasma. This study found a much higher replating efficiency for CB CFU-GEMM th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-02-15 00:00:00
abstract::A common genetic risk factor for venous thrombosis among Caucasoid subpopulations is a polymorphism, nt G1691A, in blood coagulation factor V that replaces Arg506 with Gln and imparts resistance of factor Va to the anticoagulant, activated protein C. Haplotype analyses using six dimorphic sites in the factor V gene fo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-01-15 00:00:00
abstract::Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derived peptides. Ten pat...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:
更新日期:2000-11-01 00:00:00