Increased β4GALT1 expression associates with platelet surface galactosylation and thrombopoietin plasma levels in MPNs.

Abstract:

:Aberrant megakaryopoiesis is a hallmark of the myeloproliferative neoplasms (MPNs), a group of clonal haematological malignancies originating from haematopoietic stem cells, leading to an increase in mature blood cells in the peripheral blood. Sialylated derivatives of the glycan structure β4-N-acetyllactosamine (Galβ1,4GlcNAc or type-2 LacNAc, thereafter referred to as LacNAc) regulate platelet lifespan, hepatic Thrombopoietin production, and thrombopoiesis. We found increased Thrombopoietin plasma levels in MPNs with high allele burden of the mutated clones. Remarkably, platelets isolated from MPNs had a significant increase in LacNAc expression that correlated with the high allele burden regardless of the underlying identified mutation. Megakaryocytes derived in vitro from these patients showed an increased expression of the B4GALT1 gene encoding β-1,4-galactosyltransferase1 (β4GalT1). Consistently, megakaryocytes from MPN showed increased LacNAc expression relative to healthy controls, which was counteracted by the treatment with a Janus Kinase 1/2 inhibitor. Altered expression of B4GALT1 in mutant megakaryocytes can lead to the production of platelets with aberrant galactosylation which in turn promote hepatic Thrombopoietin synthesis regardless of platelet mass. Our findings provide a new paradigm for understanding aberrant megakaryopoiesis in MPNs and identify β4GalT1 as a potential actionable target for therapy.

journal_name

Blood

journal_title

Blood

authors

Di Buduo CA,Giannini S,Abbonante V,Rosti V,Hoffmeister K,Balduini A

doi

10.1182/blood.2020007265

subject

Has Abstract

pub_date

2020-11-25 00:00:00

eissn

0006-4971

issn

1528-0020

pii

474274

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Clinical quantitation of immune signature in follicular lymphoma by RT-PCR-based gene expression profiling.

    abstract::Microarray gene expression profiling studies have demonstrated immune response gene signatures that appear predictive of outcome in follicular lymphoma (FL). However, measurement of these marker genes in routine practice remains difficult. We have therefore investigated the immune response in FL using real-time polyme...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-10-115915

    authors: Byers RJ,Sakhinia E,Joseph P,Glennie C,Hoyland JA,Menasce LP,Radford JA,Illidge T

    更新日期:2008-05-01 00:00:00

  • The anemia of chronic renal failure and chronic diseases: in vitro studies of erythropoiesis.

    abstract::The presence of a serum factor in chronic renal failure (CRF) which inhibits erythropoietin-stimulated erythropoiesis was studied, using a technique in which dog marrow cells were stimulated to produce heme in the presence of human serum. In the total series comparing 27 normal sera with 52 CRF sera, less heme was syn...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wallner SF,Kurnick JE,Ward HP,Vautrin R,Alfrey AC

    更新日期:1976-04-01 00:00:00

  • Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro.

    abstract::Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The Fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocyt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Maciejewski J,Selleri C,Anderson S,Young NS

    更新日期:1995-06-01 00:00:00

  • Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341.

    abstract::We have recently shown that proteasome inhibitor PS-341 induces apoptosis in drug-resistant multiple myeloma (MM) cells, inhibits binding of MM cells in the bone marrow microenvironment, and inhibits cytokines mediating MM cell growth, survival, drug resistance, and migration in vitro. PS-341 also inhibits human MM ce...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-08-2543

    authors: Hideshima T,Mitsiades C,Akiyama M,Hayashi T,Chauhan D,Richardson P,Schlossman R,Podar K,Munshi NC,Mitsiades N,Anderson KC

    更新日期:2003-02-15 00:00:00

  • TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies.

    abstract::Unbalanced translocations as well as interstitial deletions of the short arm of chromosome 12 [del(12p)] are found as recurring chromosomal changes in a broad spectrum of hematopoietic malignancies. These changes result in the hemizygous deletion of genetic material from 12p. We mapped a yeast artificial chromosome co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sato Y,Suto Y,Pietenpol J,Golub TR,Gilliland DG,Davis EM,Le Beau MM,Roberts JM,Vogelstein B,Rowley JD

    更新日期:1995-08-15 00:00:00

  • Decreased transfusion requirements for patients receiving nonmyeloablative compared with conventional peripheral blood stem cell transplants from HLA-identical siblings.

    abstract::Red blood cell (RBC) and platelet transfusion requirements in patients given nonmyeloablative versus conventional peripheral blood stem cell (PBSC) transplants from HLA-matched siblings were compared. Between December 1997 and March 2000, 40 patients, aged 21 to 67 years (median 51), with hematologic malignancies unde...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood.v98.13.3584

    authors: Weissinger F,Sandmaier BM,Maloney DG,Bensinger WI,Gooley T,Storb R

    更新日期:2001-12-15 00:00:00

  • Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel.

    abstract::Despite major improvements in outcome over the past decades, acute myeloid leukemia (AML) remains a life-threatening malignancy in children, with current survival rates of ∼70%. State-of-the-art recommendations in adult AML have recently been published in this journal by Döhner et al. The primary goal of an internatio...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2012-03-362608

    authors: Creutzig U,van den Heuvel-Eibrink MM,Gibson B,Dworzak MN,Adachi S,de Bont E,Harbott J,Hasle H,Johnston D,Kinoshita A,Lehrnbecher T,Leverger G,Mejstrikova E,Meshinchi S,Pession A,Raimondi SC,Sung L,Stary J,Zwaan CM,K

    更新日期:2012-10-18 00:00:00

  • Adrenergic modulation of human polymorphonuclear leukocyte activation. Potentiating effect of adenosine.

    abstract::The activation of polymorphonuclear leukocytes (PMN) is an important step in the development of tissue damage associated with inflammatory and ischemic conditions. Catecholamines have been reported to inhibit PMN functions, but the high concentrations required cast doubt on their actual relevance as a defense mechanis...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bazzoni G,Dejana E,Del Maschio A

    更新日期:1991-05-01 00:00:00

  • A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells.

    abstract::Adaptive immunity is triggered at the immune synapse, where peptide-major histocompatibility complexes and costimulatory molecules expressed by dendritic cells (DCs) are physically presented to T cells. Here we describe transmission of the inflammatory monoamine serotonin (5-hydroxytryptamine [5-HT]) between these cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-07-2903

    authors: O'Connell PJ,Wang X,Leon-Ponte M,Griffiths C,Pingle SC,Ahern GP

    更新日期:2006-02-01 00:00:00

  • Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34(+)CD38(-) progenitor cells from patients with acute myeloid leukemia.

    abstract::Efflux of Hoechst 33342 from normal hematopoietic cells identifies a "side population" (SP(+)) of negatively staining cells that, in the mouse, are largely CD34(-) and are enriched for primitive progenitors. To further characterize human SP(+) cells, blood or bone marrow from 16 patients with acute myeloid leukemia (A...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.12.3882

    authors: Feuring-Buske M,Hogge DE

    更新日期:2001-06-15 00:00:00

  • Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular

    abstract::The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HL...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-07-2365

    authors: Rimsza LM,Roberts RA,Miller TP,Unger JM,LeBlanc M,Braziel RM,Weisenberger DD,Chan WC,Muller-Hermelink HK,Jaffe ES,Gascoyne RD,Campo E,Fuchs DA,Spier CM,Fisher RI,Delabie J,Rosenwald A,Staudt LM,Grogan TM

    更新日期:2004-06-01 00:00:00

  • Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand-expressing tumor cells.

    abstract::NKG2D is an activation receptor that allows natural killer (NK) cells to detect diseased host cells. The engagement of NKG2D with corresponding ligand results in surface modulation of the receptor and reduced function upon subsequent receptor engagement. However, it is not clear whether in addition to modulation the N...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-03-0918

    authors: Coudert JD,Zimmer J,Tomasello E,Cebecauer M,Colonna M,Vivier E,Held W

    更新日期:2005-09-01 00:00:00

  • "You break it, you fix it.".

    abstract::Nonrandom chromosomal translocations are considered to be causal events leading to leukemic transformation. However, the mechanism(s) that cause these translocations are poorly understood. Libura and colleagues report exciting new findings on the mechanism(s) that lead to chromosomal translocation. ...

    journal_title:Blood

    pub_type: 评论,杂志文章,评审

    doi:10.1182/blood-2004-12-4760

    authors: Aplan PD

    更新日期:2005-03-01 00:00:00

  • Cell surface expression of c-kit receptors by childhood acute myeloid leukemia blasts is not of prognostic value: a report from the Childrens Cancer Group.

    abstract::The prognostic significance of c-kit receptor expression on leukemic blast cells was determined in 122 children with acute myeloid leukemia (AML) entered onto Childrens Cancer Group protocol 213. Clinical and laboratory characteristics as well as outcome were analyzed according to the percentage of blast cells express...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:

    authors: Smith FO,Broudy VC,Zsebo KM,Lampkin BC,Buckley CV,Buckley JD,Opie T,Woods WG,Hammond GD,Bernstein ID

    更新日期:1994-08-01 00:00:00

  • Hematopoietic progenitors and interleukin-3-dependent cell lines synthesize histamine in response to calcium ionophore.

    abstract::The calcium ionophore A23187 promotes histamine synthesis in murine bone marrow cells by increasing the expression of mRNA encoding histidine decarboxylase (HDC), the histamine-forming enzyme. The cells responsible for this biological activity copurify with hematopoietic progenitors in terms of density, light scatter ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dy M,Arnould A,Lemoine FM,Machavoine F,Ziltener H,Schneider E

    更新日期:1996-04-15 00:00:00

  • T-cell leukemias with rearrangement of the gamma but not beta T-cell receptor genes.

    abstract::beta and gamma T cell receptor (TCR) gene configuration was studied in 12 patients with large granular lymphocyte T cell leukemia (LGL-leukemia). Both genes were found rearranged in ten cases. In the remaining two patients TCR beta was found in germline configuration. In one of them rearrangement of T cell-rearranging...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Foroni L,Matutes E,Foldi J,Morilla R,Rabbitts T,Luzzatto L,Catovsky D

    更新日期:1988-02-01 00:00:00

  • The acquisition of host-derived major histocompatibility complex class II glycoproteins by human immunodeficiency virus type 1 accelerates the process of virus entry and infection in human T-lymphoid cells.

    abstract::Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely understood. However, several lines of evidence indicate that direct cytopathology mediated ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Cantin R,Fortin JF,Lamontagne G,Tremblay M

    更新日期:1997-08-01 00:00:00

  • A case-control study to assess the risk of immune thrombocytopenia associated with vaccines.

    abstract::The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hem...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2012-05-431098

    authors: Grimaldi-Bensouda L,Michel M,Aubrun E,Leighton P,Viallard JF,Adoue D,Magy-Bertrand N,Tisserand G,Khellaf M,Durand JM,Quittet P,Fain O,Bonnotte B,Morin AS,Limal N,Costedoat-Chalumeau N,Morel N,Pan-Petesch B,Decaux O,

    更新日期:2012-12-13 00:00:00

  • Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group-directed intergroup trial S9003.

    abstract::The survival of patients with Waldenstrom macroglobulinemia (WM) varies enormously. The development of prognostic models in WM has been fraught by limited follow-up in current studies. Here, we update the outcome of a prospective WM trial with a median follow-up of 10 years for live patients. Of the 59 previously untr...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2008-07-172080

    authors: Dhodapkar MV,Hoering A,Gertz MA,Rivkin S,Szymonifka J,Crowley J,Barlogie B

    更新日期:2009-01-22 00:00:00

  • Production of laminin B2 chain protein and messenger RNA by a murine neutrophil precursor cell line, 32Dc13.

    abstract::Laminin is a heterotrimeric glycoprotein that plays a central role in promoting neutrophil chemotaxis, motility, and attachment to basement membrane. Rabbit peritoneal exudate neutrophils stain positively for laminin, which is presumed to be of exogenous origin and bound to laminin receptors on the cell surface. We ex...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tweardy DJ,Sasaki M,Cardamone JJ Jr,McCoy JP Jr,Bonidie MJ,Signorella AP

    更新日期:1990-10-01 00:00:00

  • Autocrine LTA signaling drives NF-κB and JAK-STAT activity and myeloid gene expression in Hodgkin lymphoma.

    abstract::Persistent NF-κB activation is a hallmark of the malignant Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL). Genomic lesions, Epstein-Barr virus infection, soluble factors, and tumor-microenvironment interactions contribute to this activation. Here, in an unbiased approach to identify the cHL cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2018-08-871293

    authors: von Hoff L,Kärgel E,Franke V,McShane E,Schulz-Beiss KW,Patone G,Schleussner N,Kolesnichenko M,Hübner N,Daumke O,Selbach M,Akalin A,Mathas S,Scheidereit C

    更新日期:2019-03-28 00:00:00

  • Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy.

    abstract::Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2020005683

    authors: Rosen S,Tiefenbacher S,Robinson M,Huang M,Srimani J,Mackenzie D,Christianson T,Pasi KJ,Rangarajan S,Symington E,Giermasz A,Pierce GF,Kim B,Zoog SJ,Vettermann C

    更新日期:2020-11-26 00:00:00

  • Identification of 2 major loci linked to autoimmune hemolytic anemia in NZB mice.

    abstract::Using a cohort of C57BL/6 (B6) x (NZB x B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7 a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-02-0558

    authors: Kikuchi S,Amano H,Amano E,Fossati-Jimack L,Santiago-Raber ML,Moll T,Ida A,Kotzin BL,Izui S

    更新日期:2005-08-15 00:00:00

  • How I treat essential thrombocythemia.

    abstract::In the past 5 years we have witnessed significant advances in both the diagnostic process and optimal therapy for patients with essential thrombocythemia (ET). Insights into the underlying molecular mechanisms have been accompanied by the development of new diagnostic tests and by an improved understanding of the rela...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-08-270033

    authors: Beer PA,Erber WN,Campbell PJ,Green AR

    更新日期:2011-02-03 00:00:00

  • Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2.

    abstract::In childhood acute lymphoblastic leukemia (ALL), early response to treatment is a powerful prognostic indicator. To identify genes associated with this response, we analyzed gene expression of diagnostic lymphoblasts from 189 children with ALL and compared the findings with minimal residual disease (MRD) levels on day...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-01-0322

    authors: Flotho C,Coustan-Smith E,Pei D,Iwamoto S,Song G,Cheng C,Pui CH,Downing JR,Campana D

    更新日期:2006-08-01 00:00:00

  • Drug-resistant T-lymphoid tumors undergo apoptosis selectively in response to an antimicrotubule agent, EM011.

    abstract::We have shown previously that EM011, a synthetic compound, binds tubulin with a higher affinity than the founding compound, noscapine, without changing total microtubule polymer mass. Now we show that EM011 is potently effective against vinblastine-resistant human lymphoblastoid line CEM/VLB100 and its parental vinbla...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-08-3516

    authors: Aneja R,Zhou J,Vangapandu SN,Zhou B,Chandra R,Joshi HC

    更新日期:2006-03-15 00:00:00

  • Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors.

    abstract::Signaling through the Notch pathway plays an essential role in inducing T-lineage commitment and promoting the maturation of immature thymocytes. Using an in vitro culture system, we show that 2 different classes of Notch ligands, Jagged1 or Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells ex...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-08-3257

    authors: Lehar SM,Dooley J,Farr AG,Bevan MJ

    更新日期:2005-02-15 00:00:00

  • Detection of the carrier state for classic hemophilia using an enzyme-linked immunosorbent assay (ELISA).

    abstract::A high proportion of carriers of classic hemophilia can be identified in the laboratory because, in comparison to normal women, the concentration of antigens related to antihemophilic factor (AHF, factor VIII) that are detected in their plasma by heterologous antiserum (factor VIIIR:Ag) is relatively higher than the t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Fishman DJ,Jones PK,Menitove JE,Ratnoff OD,Everson B

    更新日期:1982-06-01 00:00:00

  • Long-awaited news for hepatic veno-occlusive disease.

    abstract::In this issue of Blood, Palomo et al provide new insight into the mechanism of action of defibrotide as an endothelial protective agent, while Richardson et al present the encouraging final results of the phase 3 clinical study of defibrotide for the treatment of severe hepatic veno-occlusive disease (VOD), showing a ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2016-02-694943

    authors: Arai S

    更新日期:2016-03-31 00:00:00

  • Low NAD(P)H:quinone oxidoreductase activity is associated with increased risk of leukemia with MLL translocations in infants and children.

    abstract::An inactivating polymorphism at position 609 in the NAD(P)H:quinone oxidoreductase 1 gene (NQO1 C609T) is associated with an increased risk of adult leukemia. A small British study suggested that NQO1 C609T was associated with an increased risk of infant leukemias with MLL translocations, especially infant acute lymph...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2001-12-0264

    authors: Smith MT,Wang Y,Skibola CF,Slater DJ,Lo Nigro L,Nowell PC,Lange BJ,Felix CA

    更新日期:2002-12-15 00:00:00