当前位置： SCI文献检索 > BLOOD期刊下所有文献 > Therapeutic targeting of HES1 transcriptional programs in T-ALL.

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 remain incompletely understood. Here we identify Hairy and Enhancer of Split 1 (HES1), a transcriptional repressor controlled by NOTCH1, as a critical mediator of NOTCH1-induced leukemogenesis strictly required for tumor cell survival. Mechanistically, we demonstrate that HES1 directly downregulates the expression of BBC3, the gene encoding the PUMA BH3-only proapoptotic factor in T-cell acute lymphoblastic leukemia. Finally, we identify perhexiline, a small-molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1-induced leukemias in vitro and in vivo.

journal_name

Blood

journal_title

Blood

authors

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

doi

10.1182/blood-2014-10-608448

subject

Has Abstract

pub_date

2015-04-30 00:00:00

pages

2806-14

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2014-10-608448

journal_volume

125

pub_type

杂志文章

相关文献

BLOOD文献大全
  • A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.

    abstract：:Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity ...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：

    authors： Gillan ER,Christensen RD,Suen Y,Ellis R,van de Ven C,Cairo MS

    更新日期：1994-09-01 00:00:00

  • Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis.

    abstract：:The International Prognostic Scoring System (IPSS) has been widely used to predict the prognosis of patients with myelodysplastic syndrome (MDS). However, IPSS does not always provide a sufficiently precise evaluation of patients to allow the appropriate choice of clinical interventions. Here, we analyzed the expressi...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2005-06-2393

    authors： Mihara K,Chowdhury M,Nakaju N,Hidani S,Ihara A,Hyodo H,Yasunaga S,Takihara Y,Kimura A

    更新日期：2006-01-01 00:00:00

  • Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden).

    abstract：:With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an i...

    journal_title：Blood

    pub_type： 杂志文章,多中心研究

    doi：

    authors： Faioni EM,Franchi F,Bucciarelli P,Margaglione M,De Stefano V,Castaman G,Finazzi G,Mannucci PM

    更新日期：1999-11-01 00:00:00

  • Blood tests for the diagnosis of venous and arterial thrombosis.

    abstract：:There are many reports in the literature of blood test abnormalities occurring in patients with venous or arterial thrombosis. Most of these have not used acceptable criteria for establishing an association between thrombosis and blood tests and, therefore, their interpretation is questionable. Recently, sensitive and...

    journal_title：Blood

    pub_type： 杂志文章,评审

    doi：

    authors： Hirsh J

    更新日期：1981-01-01 00:00:00

  • Hematopoietic stem cell-based gene therapy for acquired immunodeficiency syndrome: efficient transduction and expression of RevM10 in myeloid cells in vivo and in vitro.

    abstract：:Gene delivery via the hematopoietic stem cell (HSC) offers an attractive means to introduce antiviral genes into both T cells and macrophages for acquired immunodeficiency syndrome (AIDS) gene therapy. An amphotropic retroviral vector encoding a bicistronic gene coexpressing RevM10 and the murine CD8alpha' chain (lyt2...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Su L,Lee R,Bonyhadi M,Matsuzaki H,Forestell S,Escaich S,Böhnlein E,Kaneshima H

    更新日期：1997-04-01 00:00:00

  • Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells.

    abstract：:The FAS receptor-FAS ligand system is a key apoptotic pathway for cells of the immune system. Ligation of the FAS-receptor (CD95) induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species (ROS) and the release of proapoptotic factors from the mitoc...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2002-11-3559

    authors： Perez-Cruz I,Carcamo JM,Golde DW

    更新日期：2003-07-01 00:00:00

  • The role of phosphatidylinositol 3-kinase-δ in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemia.

    abstract：:In patients with chronic lymphocytic leukemia (CLL), lenalidomide can promote humoral immune responses but also induces a distinct disease-specific toxicity of tumor flare and cytokine release. These CLL-specific events result from increased expression of costimulatory molecules on B cells. Here we demonstrate that le...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2010-11-315705

    authors： Herman SE,Lapalombella R,Gordon AL,Ramanunni A,Blum KA,Jones J,Zhang X,Lannutti BJ,Puri KD,Muthusamy N,Byrd JC,Johnson AJ

    更新日期：2011-04-21 00:00:00

  • Platelet modulation of polymorphonuclear leukocyte shear induced aggregation.

    abstract：:A cone and plate viscometer and Coulter Counter were used to study platelet modulation of polymorphonuclear leukocyte (PMNL) aggregation caused by controlled shear stress. As an index of aggregation, the large-particle percentage (LPP) was calculated. This represents the ratio of aggregated cell count to total cell co...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Rhee BG,Hall ER,McIntire LV

    更新日期：1986-01-01 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

  • Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.

    abstract：:The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible fo...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2015-03-631598

    authors： Daniels G,Ballif BA,Helias V,Saison C,Grimsley S,Mannessier L,Hustinx H,Lee E,Cartron JP,Peyrard T,Arnaud L

    更新日期：2015-06-04 00:00:00

  • Thrombosis in the setting of obesity or inflammatory bowel disease.

    abstract：:Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to...

    journal_title：Blood

    pub_type： 杂志文章,评审

    doi：10.1182/blood-2016-05-716720

    authors： Lentz SR

    更新日期：2016-11-17 00:00:00

  • Thalidomide as salvage therapy for chronic graft-versus-host disease.

    abstract：:Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixt...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,多中心研究

    doi：

    authors： Parker PM,Chao N,Nademanee A,O'Donnell MR,Schmidt GM,Snyder DS,Stein AS,Smith EP,Molina A,Stepan DE,Kashyap A,Planas I,Spielberger R,Somlo G,Margolin K,Zwingenberger K,Wilsman K,Negrin RS,Long GD,Niland JC,Blume K

    更新日期：1995-11-01 00:00:00

  • Complete molecular response of e6a2 BCR-ABL-positive acute myeloid leukemia to imatinib then dasatinib.

    abstract：:De novo presentation of acute myeloid leukemia (AML) expressing the Philadelphia (Ph) chromosomal abnormality is rare and is associated with a dismal prognosis. To date, reported cases of Ph(+) AML have expressed either the e13a2 or e14a2 BCR-ABL fusion transcripts. We report a unique case of de novo AML expressing th...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2007-08-107508

    authors： Ritchie DS,McBean M,Westerman DA,Kovalenko S,Seymour JF,Dobrovic A

    更新日期：2008-03-01 00:00:00

  • Speaking a common language in MDS/MPNs.

    abstract：:In this issue of Blood, Savona and an international consortium of clinical investigators propose uniform response criteria for treatment trials enrolling adult patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Such a proposal is needed because new drugs are finally being tested in these rare “over...

    journal_title：Blood

    pub_type： 评论,杂志文章

    doi：10.1182/blood-2015-02-626473

    authors： Steensma DP

    更新日期：2015-03-19 00:00:00

  • Plasmids in bacteria exposed to activated neutrophils mediate mutagenesis when transferred to new hosts.

    abstract：:The plasmid pUC18 contains a lacZ alpha-complementation gene that codes for a small peptide that can complement the delta M15 mutation of the Escherichia coli lacZ (beta-galactosidase) gene, converting bacteria carrying that mutated gene from the lacZ- to the lacZ+ phenotype. This plasmid was used in experiments desig...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： De Togni P,Fox HB,Morrissey S,Tansey LR,Levy SB,Babior BM

    更新日期：1988-02-01 00:00:00

  • Defensin promotes the binding of lipoprotein(a) to vascular matrix.

    abstract：:Retention of lipoproteins within the vasculature is a central event in the pathogenesis of atherosclerosis. However, the signals that mediate this process are only partially understood. Prompted by putative links between inflammation and atherosclerosis, we previously reported that alpha-defensins released by neutroph...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Bdeir K,Cane W,Canziani G,Chaiken I,Weisel J,Koschinsky ML,Lawn RM,Bannerman PG,Sachais BS,Kuo A,Hancock MA,Tomaszewski J,Raghunath PN,Ganz T,Higazi AA,Cines DB

    更新日期：1999-09-15 00:00:00

  • Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors.

    abstract：:The MLL gene located at 11q23 is frequently disrupted by chromosomal translocation in a wide spectrum of newly diagnosed acute leukemias. Recently, it has become apparent that the MLL gene is very frequently disrupted by chromosomal translocations in patients with secondary leukemias associated with chemotherapeutic r...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Aplan PD,Chervinsky DS,Stanulla M,Burhans WC

    更新日期：1996-04-01 00:00:00

  • Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL.

    abstract：:Patients aged ≥60 years with treatment-naive Hodgkin lymphoma (HL) have few treatment options and inferior survival due to treatment-related toxicities and comorbidities. This phase 2, nonrandomized, open-label study evaluated brentuximab vedotin (BV) monotherapy (results previously reported), BV plus dacarbazine (DTI...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2017-06-787200

    authors： Friedberg JW,Forero-Torres A,Bordoni RE,Cline VJM,Patel Donnelly D,Flynn PJ,Olsen G,Chen R,Fong A,Wang Y,Yasenchak CA

    更新日期：2017-12-28 00:00:00

  • Elimination of acute myelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide.

    abstract：:Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells surv...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Sharkis SJ,Santos GW,Colvin M

    更新日期：1980-03-01 00:00:00

  • The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma.

    abstract：:CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombina...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2003-02-0515

    authors： Borchmann P,Treml JF,Hansen H,Gottstein C,Schnell R,Staak O,Zhang HF,Davis T,Keler T,Diehl V,Graziano RF,Engert A

    更新日期：2003-11-15 00:00:00

  • Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial.

    abstract：:All-trans retinoic acid (ATRA) is an essential component of the treatment of acute promyelocytic leukemia (APL), but the optimal timing and duration remain to be determined. Molecular characterization of this disease can refine the diagnosis and could be potentially useful in monitoring response to treatment. Patients...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：

    authors： Burnett AK,Grimwade D,Solomon E,Wheatley K,Goldstone AH

    更新日期：1999-06-15 00:00:00

  • Correction of the platelet adhesion defect in delta-storage pool deficiency at elevated hematocrit--possible role of adenosine diphosphate.

    abstract：:Previous studies on patients with storage pool deficiency (SPD) who are specifically deficient in platelet dense granules (delta-SPD) have suggested a role for dense granule substances, in all likelihood adenosine diphosphate (ADP), in mediating thrombus formation on subendothelium at high shear rates. The role of den...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Weiss HJ,Lages B,Hoffmann T,Turitto VT

    更新日期：1996-05-15 00:00:00

  • Autocrine interleukin-1 beta regulates both proliferation and apoptosis in EL4-6.1 thymoma cells.

    abstract：:We demonstrate here that EL4-6.1 cells, a mouse thymoma that expresses high levels of membrane interleukin (IL)-1 receptors, produce IL-1 beta as an autocrine regulatory factor. Endogenous IL-1 beta sustains both proliferation and apoptosis: during the exponential phase, it mainly promotes proliferation, while during ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Fratelli M,Gagliardini V,Galli G,Gnocchi P,Ghiara P,Ghezzi P

    更新日期：1995-06-15 00:00:00

  • Posttransplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus.

    abstract：:Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Frank D,Cesarman E,Liu YF,Michler RE,Knowles DM

    更新日期：1995-03-01 00:00:00

  • Gait speed, grip strength, and clinical outcomes in older patients with hematologic malignancies.

    abstract：:This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large terti...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.2019000758

    authors： Liu MA,DuMontier C,Murillo A,Hshieh TT,Bean JF,Soiffer RJ,Stone RM,Abel GA,Driver JA

    更新日期：2019-07-25 00:00:00

  • Jumping translocations of chromosome 1q in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric heterochromatin.

    abstract：:Karyotypes in multiple myeloma (MM) are complex and exhibit numerous structural and numerical aberrations. The largest subset of structural chromosome anomalies in clinical specimens and cell lines involves aberrations of chromosome 1. Unbalanced translocations and duplications involving all or part of the whole long ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Sawyer JR,Tricot G,Mattox S,Jagannath S,Barlogie B

    更新日期：1998-03-01 00:00:00

  • Hlx homeobox transcription factor negatively regulates interferon-gamma production in monokine-activated natural killer cells.

    abstract：:Natural killer (NK) cells contribute to host immunity, including tumor surveillance, through the production of interferon gamma (IFN-gamma). Although there is some knowledge about molecular mechanisms that induce IFN-gamma in NK cells, considerably less is known about the mechanisms that reduce its expression. Here, w...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2006-10-050096

    authors： Becknell B,Hughes TL,Freud AG,Blaser BW,Yu J,Trotta R,Mao HC,Caligiuri de Jesús ML,Alghothani M,Benson DM Jr,Lehman A,Jarjoura D,Perrotti D,Bates MD,Caligiuri MA

    更新日期：2007-03-15 00:00:00

  • The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines.

    abstract：:An immunosuppressant Rapamycin (Rap) has been reported to cause G1 arrest by inhibiting p70 S6 kinase and G1 cyclin/cdks kinase activities when added to quiescent cells with mitogens. However, antiproliferative effects of Rap on exponentially growing cells have been poorly investigated. We examined the intracellular e...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Kawamata S,Sakaida H,Hori T,Maeda M,Uchiyama T

    更新日期：1998-01-15 00:00:00

  • Lack of dominant-negative effects of a truncated gamma(c) on retroviral-mediated gene correction of immunodeficient mice.

    abstract：:A recent clinical trial of gene therapy for X-linked severe combined immunodeficiency (XSCID) has shown that retroviral-mediated gene correction of bone marrow stem cells can lead to the development of normal immune function. These exciting results have been preceded by successful immune reconstitution in several XSCI...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.v97.6.1618

    authors： Otsu M,Sugamura K,Candotti F

    更新日期：2001-03-15 00:00:00

  • Development of pluripotent hematopoietic progenitor cells in the human fetus.

    abstract：:Pluripotent hematopoietic progenitor cells (CFU-GEMM), myeloid progenitor cells (CFU-GM), and erythroid progenitors (BFU-E) were studied in midtrimester human fetuses using the mixed colony assay. All three progenitor cell populations were detected at high levels in the fetal liver from 12 to 23 wk of gestation. Stem ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Hann IM,Bodger MP,Hoffbrand AV

    更新日期：1983-07-01 00:00:00