Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells.

Abstract:

:We recently defined a critical role for p53 in regulating the quiescence of adult hematopoietic stem cells (HSCs) and identified necdin as a candidate p53 target gene. Necdin is a growth-suppressing protein and the gene encoding it is one of several that are deleted in patients with Prader-Willi syndrome. To define the intrinsic role of necdin in adult hematopoiesis, in the present study, we transplanted necdin-null fetal liver cells into lethally irradiated recipients. We show that necdin-null adult HSCs are less quiescent and more proliferative than normal HSCs, demonstrating the similar role of necdin and p53 in promoting HSC quiescence during steady-state conditions. However, wild-type recipients repopulated with necdin-null hematopoietic stem/progenitor cells show enhanced sensitivity to irradiation and chemotherapy, with increased p53-dependent apoptosis, myelosuppression, and mortality. Necdin controls the HSC response to genotoxic stress via both cell-cycle-dependent and cell-cycle-independent mechanisms, with the latter occurring in a Gas2L3-dependent manner. We conclude that necdin functions as a molecular switch in adult hematopoiesis, acting in a p53-like manner to promote HSC quiescence in the steady state, but suppressing p53-dependent apoptosis in response to genotoxic stress.

journal_name

Blood

journal_title

Blood

authors

Asai T,Liu Y,Di Giandomenico S,Bae N,Ndiaye-Lobry D,Deblasio A,Menendez S,Antipin Y,Reva B,Wevrick R,Nimer SD

doi

10.1182/blood-2011-11-393983

subject

Has Abstract

pub_date

2012-08-23 00:00:00

pages

1601-12

issue

8

eissn

0006-4971

issn

1528-0020

pii

blood-2011-11-393983

journal_volume

120

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Lymphoproliferative syndrome with autoimmunity: A possible genetic basis for dominant expression of the clinical manifestations.

    abstract::Fas (CD95/Apo-1) mutations were previously reported as the genetic defect responsible for human lymphoproliferative syndrome associated with autoimmune manifestations (also known as autoimmune lymphoproliferative syndrome or Canale-Smith syndrome). We have identified 14 new heterozygous Fas mutations. Analysis of pati...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rieux-Laucat F,Blachère S,Danielan S,De Villartay JP,Oleastro M,Solary E,Bader-Meunier B,Arkwright P,Pondaré C,Bernaudin F,Chapel H,Nielsen S,Berrah M,Fischer A,Le Deist F

    更新日期:1999-10-15 00:00:00

  • Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia.

    abstract::The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both col...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kelleher C,Miyauchi J,Wong G,Clark S,Minden MD,McCulloch EA

    更新日期:1987-05-01 00:00:00

  • Ligand-induced EpoR internalization is mediated by JAK2 and p85 and is impaired by mutations responsible for primary familial and congenital polycythemia.

    abstract::Epo-induced endocytosis of EpoR plays important roles in the down-regulation of EpoR signaling and is the primary means that regulates circulating Epo concentrations. Here we show that cell-surface EpoR is internalized via clathrin-mediated endocytosis. Both JAK2 kinase activity and EpoR cytoplasmic tyrosines are impo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-09-179572

    authors: Sulahian R,Cleaver O,Huang LJ

    更新日期:2009-05-21 00:00:00

  • Lipopolysaccharide induces the antiapoptotic molecules, A1 and A20, in microvascular endothelial cells.

    abstract::The effect of lipopolysaccharide (LPS) on endothelial cells is a key component of the inflammatory response seen in Gram-negative sepsis. LPS does not cause death of cultured human endothelial cells. However, when the expression of new proteins is inhibited by cycloheximide, microvascular endothelial cells in culture ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hu X,Yee E,Harlan JM,Wong F,Karsan A

    更新日期:1998-10-15 00:00:00

  • Blockade of osteopontin reduces alloreactive CD8+ T cell-mediated graft-versus-host disease.

    abstract::Graft-versus-host disease (GVHD), a life-threatening complication after allogeneic hematopoietic stem cell transplantation, is caused by alloreactive donor T cells that trigger host tissue damage. The inflammatory environment inside recipients is critical for GVHD pathogenesis, but the underpinning mechanisms remain e...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-04-281659

    authors: Zhao F,Zhang Y,Wang H,Jin M,He S,Shi Y,Guo Y,Zhang Y

    更新日期:2011-02-03 00:00:00

  • T(H)1, T(H)2, and T(H)17 cells instruct monocytes to differentiate into specialized dendritic cell subsets.

    abstract::Monocytes and T helper (T(H)) cells rapidly infiltrate inflamed tissues where monocytes differentiate into inflammatory dendritic cells (DCs) through undefined mechanisms. Our studies indicate that T(H) cells frequently interact with monocytes in inflamed skin and elicit the differentiation of specialized DC subsets c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-03-341065

    authors: Alonso MN,Wong MT,Zhang AL,Winer D,Suhoski MM,Tolentino LL,Gaitan J,Davidson MG,Kung TH,Galel DM,Nadeau KC,Kim J,Utz PJ,Söderström K,Engleman EG

    更新日期:2011-09-22 00:00:00

  • Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis.

    abstract::Gossypin, a flavone originally isolated from Hibiscus vitifolius, has been shown to suppress angiogenesis, inflammation, and carcinogenesis. The mechanisms of these activities, however, are unknown. Because nuclear factor-kappaB (NF-kappaB) is associated with inflammation, carcinogenesis, hyperproliferation, invasion,...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-01-067256

    authors: Kunnumakkara AB,Nair AS,Ahn KS,Pandey MK,Yi Z,Liu M,Aggarwal BB

    更新日期:2007-06-15 00:00:00

  • The identification and characterization of zebrafish hematopoietic stem cells.

    abstract::HSCs are defined by their ability to self-renew and maintain hematopoiesis throughout the lifespan of an organism. The optical clarity of their embryos and the ease of genetic manipulation make the zebrafish (Danio rerio) an excellent model for studying hematopoiesis. Using flow cytometry, we identified 2 populations ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-327403

    authors: Ma D,Zhang J,Lin HF,Italiano J,Handin RI

    更新日期:2011-07-14 00:00:00

  • Mitochondrial membrane sensitivity to depolarization in acute myeloblastic leukemia is associated with spontaneous in vitro apoptosis, wild-type TP53, and vicinal thiol/disulfide status.

    abstract::Nonresponse to remission-induction chemotherapy, which remains a major problem in acute myeloblastic leukemia (AML), has been linked to cellular resistance to apoptosis. Because the apoptosis induced by chemotherapeutic drugs is mediated by loss of mitochondrial transmembrane potential (MTP), it was postulated that se...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.2.405

    authors: Pallis M,Grundy M,Turzanski J,Kofler R,Russell N

    更新日期:2001-07-15 00:00:00

  • Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity.

    abstract::Myeloma is a unique hematologic malignancy that exclusively homes in the bone marrow and induces massive osteoclastic bone destruction presumably by producing cytokines that promote the differentiation of the hematopoietic progenitors to osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Michigami T,Shimizu N,Williams PJ,Niewolna M,Dallas SL,Mundy GR,Yoneda T

    更新日期:2000-09-01 00:00:00

  • Caspase-3-dependent cleavage of Bcl-xL in the stroma exosomes is required for their uptake by hematological malignant cells.

    abstract::The intercellular crosstalk between hematological malignancies and the tumor microenvironment is mediated by cell-to-cell interactions and soluble factors. One component of the secretome that is gaining increasing attention is the extracellular vesicles and, in particular, the exosomes. Apart from the role as vectors ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-05-715961

    authors: Vardaki I,Sanchez C,Fonseca P,Olsson M,Chioureas D,Rassidakis G,Ullén A,Zhivotovsky B,Björkholm M,Panaretakis T

    更新日期:2016-12-08 00:00:00

  • Proangiogenic stimulation of bone marrow endothelium engages mTOR and is inhibited by simultaneous blockade of mTOR and NF-kappaB.

    abstract::Most bone marrow (BM) malignancies develop in association with an angiogenic phenotype and increased numbers of endothelial cells. The molecular mechanisms involved in the modulation and recruitment of BM endothelium are largely unknown and may provide novel therapeutic targets for neoplastic diseases. We observed tha...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-06-2208

    authors: Costa LF,Balcells M,Edelman ER,Nadler LM,Cardoso AA

    更新日期:2006-01-01 00:00:00

  • Temperature dependence of plasmin-induced activation or inhibition of human platelets.

    abstract::It is known that at 37 degrees C plasmin may have two opposite effects on platelets: at high concentrations (greater than 1.5 caseinolytic units [CU]/mL), plasmin activates platelets; at lower concentrations (0.1 to 1.0 CU/mL) it inhibits platelet activation induced by thrombin, collagen, or calcium ionophore A23187. ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lu H,Soria C,Cramer EM,Soria J,Maclouf J,Perrot JY,Li H,Commin PL,Schumann F,Regnier O

    更新日期:1991-03-01 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

  • Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis.

    abstract::To study the role of the stress-induced "readthrough" acetylcholinesterase splice variant, AChE-R, in thrombopoiesis, we used transgenic mice overexpressing human AChE-R (TgR). Increased AChE hydrolytic activity in the peripheral blood of TgR mice was associated with increased thrombopoietin levels and platelet counts...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-08-3240

    authors: Pick M,Perry C,Lapidot T,Guimaraes-Sternberg C,Naparstek E,Deutsch V,Soreq H

    更新日期:2006-04-15 00:00:00

  • Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN.

    abstract::Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) that leads to progressive bone marrow (BM) fibrosis. Although the cellular mutations involved in the pathogenesis of PMF have been extensively investigated, the sequential events that drive stromal activation and fibrosis by hematopoietic-stromal cross...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019004095

    authors: Gleitz HFE,Dugourd AJF,Leimkühler NB,Snoeren IAM,Fuchs SNR,Menzel S,Ziegler S,Kröger N,Triviai I,Büsche G,Kreipe H,Banjanin B,Pritchard JE,Hoogenboezem R,Bindels EM,Schumacher N,Rose-John S,Elf S,Saez-Rodriguez J,Kr

    更新日期:2020-10-29 00:00:00

  • Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study.

    abstract::The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched contr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-04-347559

    authors: Lindqvist EK,Goldin LR,Landgren O,Blimark C,Mellqvist UH,Turesson I,Wahlin A,Björkholm M,Kristinsson SY

    更新日期:2011-12-08 00:00:00

  • Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.

    abstract::Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regress...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Billard C,Sigaux F,Castaigne S,Valensi F,Flandrin G,Degos L,Falcoff E,Aguet M

    更新日期:1986-03-01 00:00:00

  • Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia.

    abstract::In a patient with nonspherocytic hemolytic anemia, a hexokinase deficiency was detected in the red cells (residual activity about 25% of normal) and in blood platelets (20%-35% of normal activity). Although the total hexokinase activity in lymphocytes was normal, the amount of hexokinase type I was decreased to about ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rijksen G,Akkerman JW,van den Wall Bake AW,Hofstede DP,Staal GE

    更新日期:1983-01-01 00:00:00

  • Therapeutic targeting of HES1 transcriptional programs in T-ALL.

    abstract::Oncogenic activation of NOTCH1 signaling plays a central role in the pathogenesis of T-cell acute lymphoblastic leukemia, with mutations on this signaling pathway affecting more than 60% of patients at diagnosis. However, the transcriptional regulatory circuitries driving T-cell transformation downstream of NOTCH1 rem...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-10-608448

    authors: Schnell SA,Ambesi-Impiombato A,Sanchez-Martin M,Belver L,Xu L,Qin Y,Kageyama R,Ferrando AA

    更新日期:2015-04-30 00:00:00

  • Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia.

    abstract::The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-08-732248

    authors: Sivapalaratnam S,Westbury SK,Stephens JC,Greene D,Downes K,Kelly AM,Lentaigne C,Astle WJ,Huizinga EG,Nurden P,Papadia S,Peerlinck K,Penkett CJ,Perry DJ,Roughley C,Simeoni I,Stirrups K,Hart DP,Tait RC,Mumford AD,NI

    更新日期:2017-01-26 00:00:00

  • PIP2-dependent regulation of Munc13-4 endocytic recycling: impact on the cytolytic secretory pathway.

    abstract::Cytotoxic lymphocytes clear infected and transformed cells by releasing the content of lytic granules at cytolytic synapses, and the ability of cytolytic effectors to kill in an iterative manner has been documented previously. Although bidirectional trafficking of cytolytic machinery components along the endosomal pat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-324160

    authors: Capuano C,Paolini R,Molfetta R,Frati L,Santoni A,Galandrini R

    更新日期:2012-03-08 00:00:00

  • Effect of graft-versus-host disease on hematopoiesis after bone marrow transplantation in mice.

    abstract::We have examined the effect of graft-versus-host disease (GVHD) on the reconstitution of donor hematopoiesis in a murine bone marrow transplant (BMT) model of GVHD to minor histocompatibility antigens. GVHD had no effect on peripheral blood counts, which normalized by 1 month after BMT, and did not affect numbers of h...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: van Dijken PJ,Wimperis J,Crawford JM,Ferrara JL

    更新日期:1991-11-15 00:00:00

  • Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis.

    abstract::Selinexor is the first oral selective inhibitor of nuclear export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (#NCT03071276, #NCT02343042, #NCT02227251, #NCT0311056...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-11-752840

    authors: Machlus KR,Wu SK,Vijey P,Soussou TS,Liu ZJ,Shacham E,Unger TJ,Kashyap T,Klebanov B,Sola-Visner M,Crochiere M,Italiano JE Jr,Landesman Y

    更新日期:2017-08-31 00:00:00

  • C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function.

    abstract::We describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane-associated C7 (mC7) was indistinguishable fr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-03-146472

    authors: Bossi F,Rizzi L,Bulla R,Debeus A,Tripodo C,Picotti P,Betto E,Macor P,Pucillo C,Würzner R,Tedesco F

    更新日期:2009-04-09 00:00:00

  • The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function.

    abstract::The tetraspanin family member CD151 forms complexes with integrins and regulates cell adhesion and migration. While CD151 is highly expressed in megakaryocytes and to a lesser extent in platelets, its physiologic role in platelets is unclear. In this study, we investigate the physical and functional importance of CD15...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-12-4430

    authors: Lau LM,Wee JL,Wright MD,Moseley GW,Hogarth PM,Ashman LK,Jackson DE

    更新日期:2004-10-15 00:00:00

  • Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia.

    abstract::Typical acute promyelocytic leukemia (APL) is associated with expression of the PML-RARalpha fusion protein and responsiveness to treatment with all-trans retinoic acid (ATRA). A rare, but recurrent, APL has been described that does not respond to ATRA treatment and is associated with a variant chromosomal translocati...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Guidez F,Ivins S,Zhu J,Söderström M,Waxman S,Zelent A

    更新日期:1998-04-15 00:00:00

  • Granulated T cell lymphocytosis with neutropenia: malignant or benign chronic lymphoproliferative disorder?

    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:

    authors: McKenna RW,Arthur DC,Gajl-Peczalska KJ,Flynn P,Brunning RD

    更新日期:1985-08-01 00:00:00

  • Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).

    abstract::Optimal dose and timing of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for aggressive non-Hodgkin lymphoma (NHL) is still an unresolved issue. We assessed whether dose intensifications with cyclophosphamide and doxorubicin might improve outcome in younger patients with intermediate-r...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2006-07-035709

    authors: Verdonck LF,Notenboom A,de Jong DD,MacKenzie MA,Verhoef GE,Kramer MH,Ossenkoppele GJ,Doorduijn JK,Sonneveld P,van Imhoff GW

    更新日期:2007-04-01 00:00:00

  • alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner.

    abstract::To define the role of the alpha2beta1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and alpha2-null mice. Our findings reveal that the alpha2beta1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-06-094680

    authors: Zhang Z,Ramirez NE,Yankeelov TE,Li Z,Ford LE,Qi Y,Pozzi A,Zutter MM

    更新日期:2008-02-15 00:00:00