当前位置： SCI文献检索 > BLOOD期刊下所有文献 > A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor.

A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor.

Abstract：

:The mechanisms responsible for the low factor VIII (fVIII) activity in the plasma of patients with mild/moderate hemophilia A are poorly understood. In such patients, we have identified a series of fVIII mutations (Ile2098Ser, Ser2119Tyr, Asn2129Ser, Arg2150His, and Pro2153Gln) clustered in the C1 domain and associated with reduced binding of fVIII to von Willebrand factor (vWf). For each patient plasma, the specific activity of mutated fVIII was close to that of normal fVIII. Scatchard analysis showed that the affinity for vWf of recombinant Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII mutants was reduced 8-fold, 80-fold, and 3-fold, respectively, when compared with normal fVIII. Given the importance of vWf for the stability of fVIII in plasma, these findings suggested that the reduction of fVIII binding to vWf resulting from the above-mentioned mutations could contribute to patients' low fVIII plasma levels. We, therefore, analyzed the effect of vWf on fVIII production by Chinese hamster ovary (CHO) cells transfected with expression vectors for recombinant B domain-deleted normal, Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII. These 3 mutations impaired the vWf-dependent accumulation of functional fVIII in culture medium. Analysis of fVIII production by transiently transfected CHO cells indicated that, in addition to the impaired stabilization by vWf, the secretion of functional Ile2098Ser and Arg2150His fVIII was reduced about 2-fold and 6-fold, respectively, by comparison to Ser2119Tyr and normal fVIII. These findings indicate that C1-domain mutations resulting in reduced fVIII binding to vWf are an important cause of mild/moderate hemophilia A.

journal_name

Blood

journal_title

Blood

authors

Jacquemin M,Lavend'homme R,Benhida A,Vanzieleghem B,d'Oiron R,Lavergne JM,Brackmann HH,Schwaab R,VandenDriessche T,Chuah MK,Hoylaerts M,Gilles JG,Peerlinck K,Vermylen J,Saint-Remy JM

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

958-65

issue

3

eissn

0006-4971

issn

1528-0020

journal_volume

96

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated CLL cells by selectively activating AKT.

    abstract：:A polymorphic variant of the phosphatase PTPN22 has been associated with increased risk for multiple autoimmune diseases. The risk allele is thought to function by diminishing antigen-receptor signals responsible for negative selection of autoreactive lymphocytes. We now show that PTPN22 is markedly overexpressed in c...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2012-01-403162

    authors： Negro R,Gobessi S,Longo PG,He Y,Zhang ZY,Laurenti L,Efremov DG

    更新日期：2012-06-28 00:00:00

  • Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin.

    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：

    authors： Gentile P,Broxmeyer HE

    更新日期：1983-05-01 00:00:00

  • Regulation of early human hematopoietic (BFU-E and CFU-GEMM) progenitor cells in vitro by interleukin 1-induced fibroblast-conditioned medium.

    abstract：:Stimulators of human erythroid burst-forming units (BFU-E) and multipotential colony-forming cells (CFU-GEMM) can be produced by a number of different cell types. A product of human peripheral blood monocytes, interleukin 1 (IL-1), was evaluated for its ability to stimulate fibroblast cultures to produce stimulators o...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Zucali JR,Broxmeyer HE,Dinarello CA,Gross MA,Weiner RS

    更新日期：1987-01-01 00:00:00

  • NF-kappaB constitutes a potential therapeutic target in high-risk myelodysplastic syndrome.

    abstract：:Myelodysplastic syndrome (MDS) is a preneoplastic condition that frequently develops into overt acute myeloid leukemia (AML). The P39 MDS/AML cell line manifested constitutive NF-kappaB activation. In this cell line, NF-kappaB inhibition by small interfering RNAs specific for p65 or chemical inhibitors including borte...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2005-05-1989

    authors： Braun T,Carvalho G,Coquelle A,Vozenin MC,Lepelley P,Hirsch F,Kiladjian JJ,Ribrag V,Fenaux P,Kroemer G

    更新日期：2006-02-01 00:00:00

  • Effect of age on second messenger generation in neutrophils.

    abstract：:Neutrophils from healthy elderly donors generate significantly less diacylglycerol (DAG) and inositol triphosphate (IP3) than neutrophils from young donors, following stimulation by the chemotactic peptide, formyl-methionyl-leucylphenylalanine (FMLP). The defect in signal transduction occurred at a point proximal to t...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Lipschitz DA,Udupa KB,Indelicato SR,Das M

    更新日期：1991-09-01 00:00:00

  • Bryostatin 1, a unique biologic response modifier: anti-leukemic activity in vitro.

    abstract：:Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, has demonstrated both antineoplastic activity against the murine P388 leukemia line in vivo and stimulatory activity against mouse and human hematopoietic progenitors. We studied the effects of bryostatin 1 on the growth of human le...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Jones RJ,Sharkis SJ,Miller CB,Rowinsky EK,Burke PJ,May WS

    更新日期：1990-03-15 00:00:00

  • Regulatory control of the terminal complement proteins at the surface of human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to CD59.

    abstract：:Functionally inhibitory antibody to the plasma membrane complement inhibitor CD59 has been used to investigate control of the terminal complement proteins at the endothelial cell surface. Antibodies against purified human erythrocyte CD59 (polyclonal anti-CD59 and monoclonal antibodies [MoAbs] 1F1 and 1F5) were found ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Hamilton KK,Ji Z,Rollins S,Stewart BH,Sims PJ

    更新日期：1990-12-15 00:00:00

  • Circulating peripheral blood plasma cells as a prognostic indicator in patients with primary systemic amyloidosis.

    abstract：:This study examined the prognostic value of circulating peripheral blood plasma cells (PBPCs) in patients with primary systemic amyloidosis (AL). A sensitive slide-based immunofluorescence technique was used to assess 147 patients for circulating PBPCs. Circulating monoclonal plasma cells were quantified as a percenta...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2002-06-1698

    authors： Pardanani A,Witzig TE,Schroeder G,McElroy EA,Fonseca R,Dispenzieri A,Lacy MQ,Lust JA,Kyle RA,Greipp PR,Gertz MA,Rajkumar SV

    更新日期：2003-02-01 00:00:00

  • Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up.

    abstract：:Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase 1 testing in relapsed/refractory hairy cell leukemia (HCL; n = 28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 dose...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2017-09-803072

    authors： Kreitman RJ,Tallman MS,Robak T,Coutre S,Wilson WH,Stetler-Stevenson M,FitzGerald DJ,Santiago L,Gao G,Lanasa MC,Pastan I

    更新日期：2018-05-24 00:00:00

  • Role of nitric oxide in the anti-tumoral effect of retinoic acid and 1,25-dihydroxyvitamin D3 on human promonocytic leukemic cells.

    abstract：:All trans retinoic acid and vitamin D3 derivatives are well known for their antileukemic activity, while the precise mechanism of this effect remains to be clarified. Using human leukemic U937 and THP-1 promonocytic cell lines, we analyzed the effect of all-trans retinoic acid (RA) and/or 1,25-dihydroxyvitamin D3 (VD)...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Dugas N,Mossalayi MD,Calenda A,Léotard A,Bécherel P,Mentz F,Ouaaz F,Arock M,Debré P,Dornand J,Dugas B

    更新日期：1996-11-01 00:00:00

  • Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

    abstract：:Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effe...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2009-08-239632

    authors： Lavazza C,Carlo-Stella C,Giacomini A,Cleris L,Righi M,Sia D,Di Nicola M,Magni M,Longoni P,Milanesi M,Francolini M,Gloghini A,Carbone A,Formelli F,Gianni AM

    更新日期：2010-03-18 00:00:00

  • Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects.

    abstract：:Ras-related C3 botulinum toxin substrate 2 (RAC2), through interactions with reduced NAD phosphate oxidase component p67 phox , activates neutrophil superoxide production, whereas interactions with p21-activated kinase are necessary for fMLF-induced actin remodeling. We id...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2018-11-886028

    authors： Hsu AP,Donkó A,Arrington ME,Swamydas M,Fink D,Das A,Escobedo O,Bonagura V,Szabolcs P,Steinberg HN,Bergerson J,Skoskiewicz A,Makhija M,Davis J,Foruraghi L,Palmer C,Fuleihan RL,Church JA,Bhandoola A,Lionakis MS,Camp

    更新日期：2019-05-02 00:00:00

  • Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns.

    abstract：:Chronic lymphocytic leukemia is characterized by relapse after treatment and chemotherapy resistance. Similarly, in other malignancies leukemia cells accumulate mutations during growth, forming heterogeneous cell populations that are subject to Darwinian selection and may respond differentially to treatment. There is ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2012-05-433540

    authors： Schuh A,Becq J,Humphray S,Alexa A,Burns A,Clifford R,Feller SM,Grocock R,Henderson S,Khrebtukova I,Kingsbury Z,Luo S,McBride D,Murray L,Menju T,Timbs A,Ross M,Taylor J,Bentley D

    更新日期：2012-11-15 00:00:00

  • Characterization of monoclonal antibodies that recognize canine CD34.

    abstract：:Using a polyclonal antiserum against canine CD34, we previously found that CD34 is expressed on canine bone marrow progenitor cells in a manner analogous to that found in humans. To further characterize CD34+ cells and to facilitate preclinical canine stem cell transplant studies, monoclonal antibodies (MoAbs) were ra...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： McSweeney PA,Rouleau KA,Wallace PM,Bruno B,Andrews RG,Krizanac-Bengez L,Sandmaier BM,Storb R,Wayner E,Nash RA

    更新日期：1998-03-15 00:00:00

  • Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial.

    abstract：:In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in p...

    journal_title：Blood

    pub_type： 杂志文章,随机对照试验

    doi：10.1182/blood-2010-08-300863

    authors： Moreau P,Attal M,Pégourié B,Planche L,Hulin C,Facon T,Stoppa AM,Fuzibet JG,Grosbois B,Doyen C,Ketterer N,Sebban C,Kolb B,Chaleteix C,Dib M,Voillat L,Fontan J,Garderet L,Jaubert J,Mathiot C,Esseltine D,Avet-Loise

    更新日期：2011-03-17 00:00:00

  • How I treat disseminated intravascular coagulation.

    abstract：:Disseminated intravascular coagulation (DIC) is a condition characterized by systemic activation of coagulation, potentially leading to thrombotic obstruction of small and midsize vessels, thereby contributing to organ dysfunction. At the same time, ongoing consumption of platelets and coagulation proteins results in ...

    journal_title：Blood

    pub_type： 杂志文章,评审

    doi：10.1182/blood-2017-10-804096

    authors： Levi M,Scully M

    更新日期：2018-02-22 00:00:00

  • Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas.

    abstract：:The incidence of follicular lymphoma (FL) in industrialized countries has been increasing since the 1950s. Polymorphisms in genes encoding key enzymes controlling folate-methionine metabolism, including methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS or MTR), serine hydroxymethyltransferase (SHMT)...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2005-04-1567

    authors： Niclot S,Pruvot Q,Besson C,Savoy D,Macintyre E,Salles G,Brousse N,Varet B,Landais P,Taupin P,Junien C,Baudry-Bluteau D

    更新日期：2006-07-01 00:00:00

  • Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta-chain gene causing activation of cryptic splice sites.

    abstract：:Congenital afibrinogenemia is a rare inherited coagulopathy, characterized by very low or unmeasurable plasma levels of immunoreactive fibrinogen. So far, 25 mutations have been identified in afibrinogenemia, 17 in the Aalpha, 6 in the gamma, and only 2 in the Bbeta fibrinogen-chain genes. Here, 2 afibrinogenemic prob...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2002-06-1647

    authors： Spena S,Duga S,Asselta R,Malcovati M,Peyvandi F,Tenchini ML

    更新日期：2002-12-15 00:00:00

  • L-arginine availability regulates T-lymphocyte cell-cycle progression.

    abstract：:L-arginine (L-Arg) plays a central role in several biologic systems including the regulation of T-cell function. L-Arg depletion by myeloid-derived suppressor cells producing arginase I is seen in patients with cancer inducing T-cell anergy. We studied how L-Arg starvation could regulate T-cell-cycle progression. Stim...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2006-06-031856

    authors： Rodriguez PC,Quiceno DG,Ochoa AC

    更新日期：2007-02-15 00:00:00

  • Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome.

    abstract：:We examined the prevalence and prognostic relevance of bone marrow reticulin fibrosis in 526 patients with World Health Organization-defined polycythemia vera evaluated at the time of initial diagnosis. Seventy-four patients (14%) displayed mostly grade 1 reticulin fibrosis, with only 2 cases showing higher-grade fibr...

    journal_title：Blood

    pub_type： 杂志文章,多中心研究

    doi：10.1182/blood-2011-11-393819

    authors： Barbui T,Thiele J,Passamonti F,Rumi E,Boveri E,Randi ML,Bertozzi I,Marino F,Vannucchi AM,Pieri L,Rotunno G,Gisslinger H,Gisslinger B,Müllauer L,Finazzi G,Carobbio A,Gianatti A,Ruggeri M,Nichele I,D'Amore E,Rambald

    更新日期：2012-03-08 00:00:00

  • Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation.

    abstract：:Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS pati...

    journal_title：Blood

    pub_type： 杂志文章,多中心研究

    doi：10.1182/blood-2007-03-076679

    authors： Ozsahin H,Cavazzana-Calvo M,Notarangelo LD,Schulz A,Thrasher AJ,Mazzolari E,Slatter MA,Le Deist F,Blanche S,Veys P,Fasth A,Bredius R,Sedlacek P,Wulffraat N,Ortega J,Heilmann C,O'Meara A,Wachowiak J,Kalwak K,Matthes-

    更新日期：2008-01-01 00:00:00

  • flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions.

    abstract：:Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming growth factor-beta1 (TGF-beta1) in the induction of in vitro dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum-free cult...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Strobl H,Bello-Fernandez C,Riedl E,Pickl WF,Majdic O,Lyman SD,Knapp W

    更新日期：1997-08-15 00:00:00

  • Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma.

    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

    authors： Choi C,Witzens M,Bucur M,Feuerer M,Sommerfeldt N,Trojan A,Ho A,Schirrmacher V,Goldschmidt H,Beckhove P

    更新日期：2005-03-01 00:00:00

  • Disease-associated dendritic cells respond to disease-specific antigens through the common heat shock protein receptor.

    abstract：:The most abundant intracellular proteins, heat shock proteins (HSPs), serve as molecular chaperones for regulatory and maturation pathways. Diverse families of HSPs have been shown to bind antigenic peptides and to play major roles in innate and adaptive immune responses through the common HSP receptor, CD91. HIV-1+ p...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-03-0891

    authors： Stebbing J,Gazzard B,Portsmouth S,Gotch F,Kim L,Bower M,Mandalia S,Binder R,Srivastava P,Patterson S

    更新日期：2003-09-01 00:00:00

  • Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias.

    abstract：:The c-myb proto-oncogene has been implicated in leukemogenesis, but possible mechanisms remain ill defined. To gain further insight to this process, we used transcript profiling in K562 cells expressing a dominant-negative Myb (MERT) protein. A total of 105 potential Myb gene targets were identified. Neuromedin U (NmU...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-10-3577

    authors： Shetzline SE,Rallapalli R,Dowd KJ,Zou S,Nakata Y,Swider CR,Kalota A,Choi JK,Gewirtz AM

    更新日期：2004-09-15 00:00:00

  • Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine.

    abstract：:The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5(+) CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2011-12-396648

    authors： Pallikkuth S,Parmigiani A,Silva SY,George VK,Fischl M,Pahwa R,Pahwa S

    更新日期：2012-08-02 00:00:00

  • Lack of Fc-epsilon receptors on murine eosinophils: implications for the functional significance of elevated IgE and eosinophils in parasitic infections.

    abstract：:Chronic infection with Schistosoma mansoni induces in humans and mice a Th2-dominant immune response in which eosinophils and IgE are conspicuously elevated. Human eosinophils express IgE receptors that participate in an IgE-dependent eosinophil-mediated ADCC reaction against Schistosomula larvae in vitro. To investig...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： de Andres B,Rakasz E,Hagen M,McCormik ML,Mueller AL,Elliot D,Metwali A,Sandor M,Britigan BE,Weinstock JV,Lynch RG

    更新日期：1997-05-15 00:00:00

  • The rhesus macaque as an animal model for hemophilia B gene therapy.

    abstract：:We have determined the 2905 nucleotide sequence of the rhesus macaque factor IX complementary DNA (cDNA) and found it to be greater than 95% identical to that of the human factor IX cDNA. The cDNA has a large 3' untranslated region like the human cDNA, but unlike the human cDNA has two polyadenylation sites 224 nucleo...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Lozier JN,Metzger ME,Donahue RE,Morgan RA

    更新日期：1999-03-15 00:00:00

  • Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML.

    abstract：:In 2017, 4 drugs received US Food and Drug Administration marketing approval for acute myeloid leukemia (AML) treatment: targeted therapies for mutant FLT3 and IDH2, a liposomal cytarabine-daunorubicin formulation for therapy-related AML and AML with myelodysplasia-related changes, and resurgence of an antibody-drug c...

    journal_title：Blood

    pub_type： 杂志文章,评审

    doi：10.1182/blood-2017-08-784066

    authors： Wei AH,Tiong IS

    更新日期：2017-12-07 00:00:00

  • Monoclonal antibody 7G3 recognizes the N-terminal domain of the human interleukin-3 (IL-3) receptor alpha-chain and functions as a specific IL-3 receptor antagonist.

    abstract：:The human interleukin-3 receptor (IL-3R) is expressed on myeloid, lymphoid, and vascular endothelial cells, where it transduces IL-3-dependent signals leading to cell activation. Although IL-3R activation may play a role in hematopoiesis and immunity, its aberrant expression or excessive stimulation may contribute to ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Sun Q,Woodcock JM,Rapoport A,Stomski FC,Korpelainen EI,Bagley CJ,Goodall GJ,Smith WB,Gamble JR,Vadas MA,Lopez AF

    更新日期：1996-01-01 00:00:00