Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency.

Abstract:

:Early B-cell factor 1 (Ebf1) is a transcription factor with documented dose-dependent functions in normal and malignant B-lymphocyte development. To understand more about the roles of Ebf1 in malignant transformation, we investigated the impact of reduced functional Ebf1 dosage on mouse B-cell progenitors. Gene expression analysis suggested that Ebf1 was involved in the regulation of genes important for DNA repair and cell survival. Investigation of the DNA damage in steady state, as well as after induction of DNA damage by UV light, confirmed that pro-B cells lacking 1 functional allele of Ebf1 display signs of increased DNA damage. This correlated to reduced expression of DNA repair genes including Rad51, and chromatin immunoprecipitation data suggested that Rad51 is a direct target for Ebf1. Although reduced dosage of Ebf1 did not significantly increase tumor formation in mice, a dramatic increase in the frequency of pro-B cell leukemia was observed in mice with combined heterozygous mutations in the Ebf1 and Pax5 genes, revealing a synergistic effect of combined dose reduction of these proteins. Our data suggest that Ebf1 controls DNA repair in a dose-dependent manner providing a possible explanation to the frequent involvement of EBF1 gene loss in human leukemia.

journal_name

Blood

journal_title

Blood

authors

Prasad MA,Ungerbäck J,Åhsberg J,Somasundaram R,Strid T,Larsson M,Månsson R,De Paepe A,Lilljebjörn H,Fioretos T,Hagman J,Sigvardsson M

doi

10.1182/blood-2014-12-617282

subject

Has Abstract

pub_date

2015-06-25 00:00:00

pages

4052-9

issue

26

eissn

0006-4971

issn

1528-0020

pii

blood-2014-12-617282

journal_volume

125

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder.

    abstract::Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by deplet...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Vie H,Chevalier S,Garand R,Moisan JP,Praloran V,Devilder MC,Moreau JF,Soulillou JP

    更新日期:1989-07-01 00:00:00

  • CD40 activation does not protect chronic lymphocytic leukemia B cells from apoptosis induced by cytotoxic T lymphocytes.

    abstract::Cytotoxic T lymphocytes (CTLs) can kill target cells by the granule/exocytosis pathway or the Fas-mediated apoptosis pathway. The sensitivity of chronic lymphocytic leukemia (CLL) B cells to CTL-mediated apoptosis before and after CD40 activation was examined. Resting or CD40-activated CLL cells were found to be equal...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chu P,Wierda WG,Kipps TJ

    更新日期:2000-06-15 00:00:00

  • Intragenic Factor IX restriction site polymorphism in hemophilia B variants.

    abstract::This study includes 47 normal subjects and 25 hemophilia B patients without inhibitor(s), showing different factor IX coagulant activity and antigen levels. Genomic DNA, digested with various restriction endonucleases, was hybridized with two different factor IX probes, ie, the cDNA and the subgenomic probe for the in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hassan HJ,Orlando M,Leonardi A,Chelucci C,Guerriero R,Mannucci PM,Mariani G,Peschle C

    更新日期:1985-02-01 00:00:00

  • Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus.

    abstract::Immune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression o...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-02-202655

    authors: Poonia B,Salvato MS,Yagita H,Maeda T,Okumura K,Pauza CD

    更新日期:2009-08-06 00:00:00

  • Umbilical cord blood transplantation and cytomegalovirus: Posttransplantation infection and donor screening.

    abstract::This study assessed the incidence of cytomegalovirus (CMV) infection after transplantation of cord blood (CB) from unrelated donors and evaluated strategies for screening CB donors. Posttransplantation CMV infection, reported in 23% of 1221 CB recipients, was associated with patient pretransplantation CMV serology (P ...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2006-04-020313

    authors: Albano MS,Taylor P,Pass RF,Scaradavou A,Ciubotariu R,Carrier C,Dobrila L,Rubinstein P,Stevens CE

    更新日期:2006-12-15 00:00:00

  • Hemopoietic lineage commitment decisions: in vivo evidence from a transgenic mouse model harboring micro LCR-betapro-LacZ as a transgene.

    abstract::A substantial body of published data suggests activation of lineage-specific genes in multipotential hemopoietic cells before their unilineage commitment. Because the behavior and plasticity of cells isolated in vitro away from microenvironmental constraints exercised in vivo may be altered, one wonders whether simila...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Papayannopoulou T,Priestley GV,Rohde A,Peterson KR,Nakamoto B

    更新日期:2000-02-15 00:00:00

  • In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta).

    abstract::Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets am...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Musial J,Niewiarowski S,Edmunds LH Jr,Addonizio VP Jr,Nicolaou KC,Colman RW

    更新日期:1980-10-01 00:00:00

  • A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels.

    abstract::Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. B...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2006-06-026104

    authors: Viel KR,Machiah DK,Warren DM,Khachidze M,Buil A,Fernstrom K,Souto JC,Peralta JM,Smith T,Blangero J,Porter S,Warren ST,Fontcuberta J,Soria JM,Flanders WD,Almasy L,Howard TE

    更新日期:2007-05-01 00:00:00

  • Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apoptosis.

    abstract::Eosinophils are associated with type 2 immune responses to allergens and helminths. They release various proinflammatory mediators and toxic proteins on activation and are therefore considered proinflammatory effector cells. Eosinophilia is promoted by the cytokines interleukin (IL)-3, IL-5, and granulocyte macrophage...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-10-607788

    authors: Schwartz C,Willebrand R,Huber S,Rupec RA,Wu D,Locksley R,Voehringer D

    更新日期:2015-06-18 00:00:00

  • Morphological analysis of microparticle generation in heparin-induced thrombocytopenia.

    abstract::Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication of heparin use. HIT sera can generate platelet-derived microparticles, which are produced in a heparin-dependent manner and are hypothesized to be important initial pathological participants because they promote vascular occlusion. To dat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hughes M,Hayward CP,Warkentin TE,Horsewood P,Chorneyko KA,Kelton JG

    更新日期:2000-07-01 00:00:00

  • Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses.

    abstract::Fifty patients with Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML) in early chronic phase received imatinib mesylate, 400 mg orally daily. After a median follow-up of 9 months, 49 patients (98%) achieved a complete hematologic response and 45 patients (90%) achieved a major cytogenetic res...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2002-02-0545

    authors: Kantarjian HM,Cortes JE,O'Brien S,Giles F,Garcia-Manero G,Faderl S,Thomas D,Jeha S,Rios MB,Letvak L,Bochinski K,Arlinghaus R,Talpaz M

    更新日期:2003-01-01 00:00:00

  • The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes.

    abstract::Global gene expression profiling of highly purified 5q-deleted CD34+CD38(-)Thy1+ cells in 5q- myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38(-)Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-03-079368

    authors: Nilsson L,Edén P,Olsson E,Månsson R,Astrand-Grundström I,Strömbeck B,Theilgaard-Mönch K,Anderson K,Hast R,Hellström-Lindberg E,Samuelsson J,Bergh G,Nerlov C,Johansson B,Sigvardsson M,Borg A,Jacobsen SE

    更新日期:2007-10-15 00:00:00

  • Hematopoiesis on cellulose ester membranes. XI. Induction of new bone and a hematopoietic microenvironment by matrix factors secreted by marrow stromal cells.

    abstract::Cellulose ester membranes (CEM) were coated with stromal cells from bone marrow (BM) or bone and implanted intraperitoneally (IP) in CAF1 mice for intervals of 1 to 6 months. Previous studies indicated that matrix factors [glycoproteins (GPs), proteoglycans (PGs), and glycosaminoglycans (GAGs)] were secreted by the re...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Knospe WH,Husseini SG,Fried W

    更新日期:1989-07-01 00:00:00

  • Use of scid mice to identify and quantitate lymphoid-restricted stem cells in long-term bone marrow cultures.

    abstract::Mice homozygous for an autosomal recessive scid (severe combined immune deficiency) mutation on chromosome 16 exhibit a defect that specifically impairs lymphoid differentiation but not myelopoiesis. Consequently such mice are deficient in both humoral and cell-mediated immune functions. Despite their defect, scid mic...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Fulop GM,Phillips RA

    更新日期:1989-10-01 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

  • The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development.

    abstract::Signaling mediated by various Notch receptors and their ligands regulates diverse biological processes, including lymphoid cell fate decisions. Notch1 is required during T-cell development, while Notch2 and the Notch ligand Delta-like1 control marginal zone B (MZB) cell development. We previously determined that Maste...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-06-097030

    authors: Wu L,Maillard I,Nakamura M,Pear WS,Griffin JD

    更新日期:2007-11-15 00:00:00

  • Interleukin-24 inhibits the plasma cell differentiation program in human germinal center B cells.

    abstract::Complex molecular mechanisms control B-cell fate to become a memory or a plasma cell. Interleukin-24 (IL-24) is a class II family cytokine of poorly understood immune function that regulates the cell cycle. We previously observed that IL-24 is strongly expressed in leukemic memory-type B cells. Here we show that IL-24...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-05-220251

    authors: Maarof G,Bouchet-Delbos L,Gary-Gouy H,Durand-Gasselin I,Krzysiek R,Dalloul A

    更新日期:2010-03-04 00:00:00

  • Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6.

    abstract::Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (enco...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-07-295147

    authors: Lenoir A,Deschemin JC,Kautz L,Ramsay AJ,Roth MP,Lopez-Otin C,Vaulont S,Nicolas G

    更新日期:2011-01-13 00:00:00

  • Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses.

    abstract::The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-07-2283

    authors: Li HY,Appelbaum FR,Willman CL,Zager RA,Banker DE

    更新日期:2003-05-01 00:00:00

  • Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors.

    abstract::Merkel cell polyomavirus (MCPyV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-09-310557

    authors: Pancaldi C,Corazzari V,Maniero S,Mazzoni E,Comar M,Martini F,Tognon M

    更新日期:2011-06-30 00:00:00

  • Lack of alpha2-antiplasmin promotes pulmonary heart failure via overrelease of VEGF after acute myocardial infarction.

    abstract::Identification of a novel therapy for prevention of sudden death by ischemic cardiac infarction is an area of intensive investigation. We here report that the mortality due to an experimental acute myocardial infarction (AMI) was markedly increased in mice deficient in alpha2-antiplasmin (alpha2-AP(-/-) mice) but not ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2001-12-0251

    authors: Matsuno H,Kozawa O,Yoshimi N,Akamatsu S,Hara A,Mori H,Okada K,Ueshima S,Matsuo O,Uematsu T

    更新日期:2002-10-01 00:00:00

  • Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial.

    abstract::Immune function has been restored in 9 of 10 children with X-linked severe combined immunodeficiency by gamma c gene transfer in CD34+ cells. The distribution of both T-cell receptor (TCR) V beta family usage and TCR V beta complementarity-determining region 3 (CDR3) length revealed a broadly diversified T-cell repert...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2004-07-2648

    authors: Schmidt M,Hacein-Bey-Abina S,Wissler M,Carlier F,Lim A,Prinz C,Glimm H,Andre-Schmutz I,Hue C,Garrigue A,Le Deist F,Lagresle C,Fischer A,Cavazzana-Calvo M,von Kalle C

    更新日期:2005-04-01 00:00:00

  • Deformability measurements on individual sickle cells using a new system with pO2 and temperature control.

    abstract::Although the rheologic behavior of sickle erythrocytes (SS cells) is highly dependent on oxygen tension (pO2) and temperature, very little data exist regarding the effects of deoxygenation and reoxygenation on the rheology of "individual" SS cells at body temperature. We have devised and assessed a new experiment syst...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Itoh T,Chien S,Usami S

    更新日期:1992-04-15 00:00:00

  • Sequence variations in the 5' flanking and IVS-II regions of the G gamma- and A gamma-globin genes of beta S chromosomes with five different haplotypes.

    abstract::We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lanclos KD,Oner C,Dimovski AJ,Gu YC,Huisman TH

    更新日期:1991-06-01 00:00:00

  • Minimal region of loss at 13q14 in B-cell chronic lymphocytic leukemia.

    abstract::Allelic loss at nonrandom chromosomal sites is thought to mark the position of tumor suppressor genes involved in the pathogenesis and progression of human malignancies. Solid tumors in particular have been found to harbor multiple genetic changes resulting in loss of function mutations. Tumor suppressor genes have al...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bullrich F,Veronese ML,Kitada S,Jurlander J,Caligiuri MA,Reed JC,Croce CM

    更新日期:1996-10-15 00:00:00

  • Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial.

    abstract::This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patie...

    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:

    authors: Ottmann OG,Hoelzer D,Gracien E,Ganser A,Kelly K,Reutzel R,Lipp T,Busch FW,Schwonzen M,Heil G

    更新日期:1995-07-15 00:00:00

  • VH gene analysis of clonally related IgM and IgG from human lymphoplasmacytoid B-cell tumors with chronic lymphocytic leukemia features and high serum monoclonal IgG.

    abstract::An unusual group of human B-cell tumors with cellular features of chronic lymphocytic leukemia or lymphoplasmacytoid leukemia, together with high levels of a monoclonal IgG serum protein, has been investigated. Analysis of tumor-derived VH genes of neoplastic B lymphocytes was used to determine the clonal relationship...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sahota SS,Garand R,Bataille R,Smith AJ,Stevenson FK

    更新日期:1998-01-01 00:00:00

  • Erythropoiesis-inhibiting factor(s) (EIF): methodologic studies.

    abstract::Erythropoiesis-inhibiting factors (EIF) have been demonstrated in plasma from hypertransfused animals and from polycythemic individuals during periods of hyperoxia, but there is a decided discrepancy in the data published. In the present paper methodologic variations of a bioassay for demonstrating the erythropoiesis-...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lindemann R

    更新日期:1976-01-01 00:00:00

  • Murine stromal cells counteract the loss of long-term culture-initiating cell potential induced by cytokines in CD34(+)CD38(low/neg) human bone marrow cells.

    abstract::Evidence has been provided recently that shows that high concentrations of cytokines can fulfill functions previously attributed to stromal cells, such as promote the survival of, and led to a net increase in human primitive progenitors initiating long-term cultures in vitro (LTC-IC) or engrafting NOD-SCID (nonobese d...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bennaceur-Griscelli A,Tourino C,Izac B,Vainchenker W,Coulombel L

    更新日期:1999-07-15 00:00:00

  • Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase-dependent induction of Socs-3.

    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

    authors: Caruso R,Stolfi C,Sarra M,Rizzo A,Fantini MC,Pallone F,MacDonald TT,Monteleone G

    更新日期:2009-04-09 00:00:00