当前位置： SCI文献检索 > BLOOD期刊下所有文献 > HHEX promotes myeloid transformation in cooperation with mutant ASXL1.

HHEX promotes myeloid transformation in cooperation with mutant ASXL1.

Abstract：

:Additional sex combs-like 1 (ASXL1), an epigenetic modulator, is frequently mutated in myeloid neoplasms. Recent analyses of mutant ASXL1 conditional knockin (ASXL1-MT-KI) mice suggested that ASXL1-MT alone is insufficient for myeloid transformation. In our previous study, we used retrovirus-mediated insertional mutagenesis, which exhibited the susceptibility of ASXL1-MT-KI hematopoietic cells to transform into myeloid leukemia cells. In this screening, we identified the hematopoietically expressed homeobox (HHEX) gene as one of the common retrovirus integration sites. In this study, we investigated the potential cooperation between ASXL1-MT and HHEX in myeloid leukemogenesis. Expression of HHEX enhanced proliferation of ASXL1-MT-expressing HSPCs by inhibiting apoptosis and blocking differentiation, whereas it showed only modest effect in normal HSPCs. Moreover, ASXL1-MT and HHEX accelerated the development of RUNX1-ETO9a and FLT3-ITD leukemia. Conversely, HHEX depletion profoundly attenuated the colony-forming activity and leukemogenicity of ASXL1-MT-expressing leukemia cells. Mechanistically, we identified MYB and ETV5 as downstream targets for ASXL1-MT and HHEX by using transcriptome and chromatin immunoprecipitation-next-generation sequencing analyses. Moreover, we found that expression of ASXL1-MT enhanced the binding of HHEX to the promoter loci of MYB or ETV5 via reducing H2AK119ub. Depletion of MYB or ETV5 induced apoptosis or differentiation in ASXL1-MT-expressing leukemia cells, respectively. In addition, ectopic expression of MYB or ETV5 reversed the reduced colony-forming activity of HHEX-depleted ASXL1-MT-expressing leukemia cells. These findings indicate that the HHEX-MYB/ETV5 axis promotes myeloid transformation in ASXL1-mutated preleukemia cells.

journal_name

Blood

journal_title

Blood

authors

Takeda R,Asada S,Park SJ,Yokoyama A,Becker HJ,Kanai A,Visconte V,Hershberger C,Hayashi Y,Yonezawa T,Tamura M,Fukushima T,Tanaka Y,Fukuyama T,Matsumoto A,Yamasaki S,Nakai K,Yamazaki S,Inaba T,Shibata T,Inoue D,Ho

doi

10.1182/blood.2019004613

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1670-1684

issue

14

eissn

0006-4971

issn

1528-0020

pii

460670

journal_volume

136

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Prognostic significance of Bax protein expression in diffuse aggressive non-Hodgkin's lymphoma.

    abstract：:Bax is a proapoptotic member of the Bcl-2 protein family. The incidence and prognostic significance of Bax protein expression in diffuse non-Hodgkin's lymphomas with a large cell component (DLCL) was determined by an immunohistochemical method by using paraffin-embedded tumors from a cohort of patients treated uniform...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Gascoyne RD,Krajewska M,Krajewski S,Connors JM,Reed JC

    更新日期：1997-10-15 00:00:00

  • Evidence for a pretranslational defect in hereditary and acquired myeloperoxidase deficiency.

    abstract：:Myeloperoxidase (MPO) is a heme containing enzyme involved in the oxygen-dependent microbicidal activity of human polymorphonuclear leukocytes (PMN). Complete hereditary and acquired MPO deficiencies are defined as lack of peroxidase activity in PMN. Using this criterion, we studied a patient with complete hereditary ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Tobler A,Selsted ME,Miller CW,Johnson KR,Novotny MJ,Rovera G,Koeffler HP

    更新日期：1989-05-15 00:00:00

  • Treatment of invasive streptococcal infection with a peptide derived from human high-molecular weight kininogen.

    abstract：:Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure resulting from vascular leakage are often observed in these severe conditions. In the prese...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2008-10-182527

    authors： Oehmcke S,Shannon O,von Köckritz-Blickwede M,Mörgelin M,Linder A,Olin AI,Björck L,Herwald H

    更新日期：2009-07-09 00:00:00

  • A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis.

    abstract：:The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mouse model to study the role of Hhex in adult he...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2014-06-579813

    authors： Jackson JT,Nasa C,Shi W,Huntington ND,Bogue CW,Alexander WS,McCormack MP

    更新日期：2015-01-29 00:00:00

  • Genetic basis of hemolytic anemia caused by pyrimidine 5' nucleotidase deficiency.

    abstract：:Pyrimidine 5' nucleotidase (P5'N-1) deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associa...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.v97.11.3327

    authors： Marinaki AM,Escuredo E,Duley JA,Simmonds HA,Amici A,Naponelli V,Magni G,Seip M,Ben-Bassat I,Harley EH,Thein SL,Rees DC

    更新日期：2001-06-01 00:00:00

  • Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study.

    abstract：:The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leuke...

    journal_title：Blood

    pub_type： 临床试验,杂志文章

    doi：10.1182/blood-2006-03-011908

    authors： de Labarthe A,Rousselot P,Huguet-Rigal F,Delabesse E,Witz F,Maury S,Réa D,Cayuela JM,Vekemans MC,Reman O,Buzyn A,Pigneux A,Escoffre M,Chalandon Y,MacIntyre E,Lhéritier V,Vernant JP,Thomas X,Ifrah N,Dombret H,Group

    更新日期：2007-02-15 00:00:00

  • A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display.

    abstract：:Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surfa...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2009-05-222786

    authors： Baskar S,Suschak JM,Samija I,Srinivasan R,Childs RW,Pavletic SZ,Bishop MR,Rader C

    更新日期：2009-11-12 00:00:00

  • Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.

    abstract：:The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1182/blood-2004-09-3728

    authors： Amadori S,Suciu S,Jehn U,Stasi R,Thomas X,Marie JP,Muus P,Lefrère F,Berneman Z,Fillet G,Denzlinger C,Willemze R,Leoni P,Leone G,Casini M,Ricciuti F,Vignetti M,Beeldens F,Mandelli F,De Witte T,EORTC\/GIMEMA Leukemi

    更新日期：2005-07-01 00:00:00

  • 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 (Galβ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.2020007265

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

    更新日期：2020-11-25 00:00:00

  • Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia.

    abstract：:A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly ant...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：

    authors： Gmür J,von Felten A,Osterwalder B,Honegger H,Hörmann A,Sauter C,Deubelbeiss K,Berchtold W,Metaxas M,Scali G,Frick PG

    更新日期：1983-08-01 00:00:00

  • Conditional knockout mice demonstrate function of Klf5 as a myeloid transcription factor.

    abstract：:Krüppel-like factor 5 (Klf5) encodes a zinc-finger transcription factor and has been reported to be a direct target of C/EBPα, a master transcription factor critical for formation of granulocyte-macrophage progenitors (GMP) and leukemic GMP. Using an in vivo hematopoietic-specific gene ablation model, we demonstrate t...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2015-12-684514

    authors： Shahrin NH,Diakiw S,Dent LA,Brown AL,D'Andrea RJ

    更新日期：2016-07-07 00:00:00

  • Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice.

    abstract：:Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimu...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Kawase Y,Akashi M,Ohtsu H,Aoki Y,Akanuma A,Suzuki G

    更新日期：1993-10-01 00:00:00

  • Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes.

    abstract：:CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was del...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.v98.9.2626

    authors： Wurbel MA,Malissen M,Guy-Grand D,Meffre E,Nussenzweig MC,Richelme M,Carrier A,Malissen B

    更新日期：2001-11-01 00:00:00

  • Immunocytochemical discovery of the 22- to 23-Kd subunit of cytochrome b558 at the surface of human peripheral phagocytes.

    abstract：:A monoclonal antibody raised against cytochrome b558 reacted specifically with the 22- to 23-Kd protein, the small subunit of this cytochrome. Cytochemical studies showed that the epitope was located on the surfaces of human neutrophils and monocytes. The small subunit of cytochrome b558, therefore, was expressed at l...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Nakamura M,Sendo S,van Zwieten R,Koga T,Roos D,Kanegasaki S

    更新日期：1988-11-01 00:00:00

  • Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

    abstract：:Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the rem...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2015-07-661835

    authors： Milosevic Feenstra JD,Nivarthi H,Gisslinger H,Leroy E,Rumi E,Chachoua I,Bagienski K,Kubesova B,Pietra D,Gisslinger B,Milanesi C,Jäger R,Chen D,Berg T,Schalling M,Schuster M,Bock C,Constantinescu SN,Cazzola M,Kralovi

    更新日期：2016-01-21 00:00:00

  • Molecular basis of reduced or absent expression of decay-accelerating factor in Cromer blood group phenotypes.

    abstract：:The human erythrocyte blood group system Cromer consists of high-incidence and low-incidence antigens that reside on decay-accelerating factor (DAF; CD55), a glycosyl-phosphatidylinositol-anchored membrane protein that regulates complement activation on cell surfaces. In the Cromer phenotypes Dr(a-) and Inab there is ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Lublin DM,Mallinson G,Poole J,Reid ME,Thompson ES,Ferdman BR,Telen MJ,Anstee DJ,Tanner MJ

    更新日期：1994-08-15 00:00:00

  • New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients.

    abstract：:We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) at 4 institutions in Austria and 4 in Germany. Cytogenetic analyses were successfully performed in 2072 (97.6%) patients, revealing clonal abnormaliti...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2007-03-082404

    authors： Haase D,Germing U,Schanz J,Pfeilstöcker M,Nösslinger T,Hildebrandt B,Kundgen A,Lübbert M,Kunzmann R,Giagounidis AA,Aul C,Trümper L,Krieger O,Stauder R,Müller TH,Wimazal F,Valent P,Fonatsch C,Steidl C

    更新日期：2007-12-15 00:00:00

  • An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation.

    abstract：:An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion-binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody wa...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Arnaud E,Lafay M,Gaussem P,Picard V,Jandrot-Perrus M,Aiach M,Rendu F

    更新日期：1994-09-15 00:00:00

  • Regulation of type I plasminogen activator inhibitor by fibrin degradation products in rat lung fibroblasts.

    abstract：:Persistent fibrin deposition in tissues characterizes the early pathology of many types of injury. In an animal model of bleomycin-induced lung fibrosis, increased expression of type 1 plasminogen activator inhibitor (PAI-1) is associated with accumulation of fibrin in fibroproliferative lesions. Plasmin proteolysis o...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Hagood JS,Olman MA,Godoy JA,Rivera KE,Fuller GM

    更新日期：1996-05-01 00:00:00

  • 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission.

    abstract：:In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 study in which targeted irradiation delivered by 131I-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/mL) and cyc...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2005-06-2317

    authors： Pagel JM,Appelbaum FR,Eary JF,Rajendran J,Fisher DR,Gooley T,Ruffner K,Nemecek E,Sickle E,Durack L,Carreras J,Horowitz MM,Press OW,Gopal AK,Martin PJ,Bernstein ID,Matthews DC

    更新日期：2006-03-01 00:00:00

  • Effect of interleukin-1 beta converting enzyme inhibitor on acute myelogenous leukemia progenitor proliferation.

    abstract：:Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) is a cysteine protease that specifically cleaves precursor IL-1 beta to its biologically active form. Recent studies have also implicated ICE in the induction of apoptosis in vertebrate cells. Because IL-1 plays a major role in acute myelogenous leukemia (AML) bla...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Estrov Z,Black RA,Sleath PR,Harris D,Van Q,LaPushin R,Estey EH,Talpaz M

    更新日期：1995-12-15 00:00:00

  • Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency.

    abstract：:Atypical hemolytic uremic syndrome (aHUS) is a severe renal disease that is associated with defective complement regulation caused by multiple factors. We previously described the deficiency of factor H-related proteins CFHR1 and CFHR3 as predisposing factor for aHUS. Here we identify in an extended cohort of 147 aHUS...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2007-09-109876

    authors： Józsi M,Licht C,Strobel S,Zipfel SL,Richter H,Heinen S,Zipfel PF,Skerka C

    更新日期：2008-02-01 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

  • SH2 domain-mediated targeting, but not localization, of Syk in the plasma membrane is critical for FcepsilonRI signaling.

    abstract：:Aggregation of the high-affinity IgE receptor induces the tyrosine phosphorylation of subunits of the receptor and the subsequent association with the receptor of the cytosolic protein tyrosine kinase Syk. The current experiments examined the functional importance of membrane association of Syk and the role of the SH2...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.v97.5.1352

    authors： Sada K,Zhang J,Siraganian RP

    更新日期：2001-03-01 00:00:00

  • Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation.

    abstract：:Initial molecular events leading to natural killer lymphocyte (NK) and dendritic cell (DC) interactions are largely unknown. Here, the role of CX3CL1 (fractalkine), a chemokine expressed on mature dendritic cells (mDCs) has been investigated. We show that CX3CL1 promotes NK activation by mDCs. After blocking of CX3CL1...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2007-12-126888

    authors： Pallandre JR,Krzewski K,Bedel R,Ryffel B,Caignard A,Rohrlich PS,Pivot X,Tiberghien P,Zitvogel L,Strominger JL,Borg C

    更新日期：2008-12-01 00:00:00

  • The shortest isoform of C/EBPβ, liver inhibitory protein (LIP), collaborates with Evi1 to induce AML in a mouse BMT model.

    abstract：:Ecotropic viral integration site 1 (Evi1) is one of the master regulators in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome. High expression of Evi1 is found in 10% of patients with AML and indicates a poor outcome. Several recent studies have indicated that Evi1 requires collaborative fa...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2011-07-368654

    authors： Watanabe-Okochi N,Yoshimi A,Sato T,Ikeda T,Kumano K,Taoka K,Satoh Y,Shinohara A,Tsuruta T,Masuda A,Yokota H,Yatomi Y,Takahashi K,Kitaura J,Kitamura T,Kurokawa M

    更新日期：2013-05-16 00:00:00

  • p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells.

    abstract：:ShcA is an important mediator of Ras/MAPK activation in PTK-regulated pathways triggered by surface receptors. This function is subserved by the constitutively expressed p52-kDa isoform. Besides activating Ras, p52Shc couples the TCR to Rho GTPases, and thereby participates in actin cytoskeleton remodeling in T cells....

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2007-01-068411

    authors： Patrussi L,Ulivieri C,Lucherini OM,Paccani SR,Gamberucci A,Lanfrancone L,Pelicci PG,Baldari CT

    更新日期：2007-09-15 00:00:00

  • PECAM-1-dependent neutrophil transmigration is independent of monolayer PECAM-1 signaling or localization.

    abstract：:Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a tyrosine phosphoprotein highly expressed on endothelial cells and leukocytes, is an important component in the regulation of neutrophil transendothelial migration. Engagement of endothelial PECAM-1 activates tyrosine phosphorylation events and evokes prol...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2002-08-2396

    authors： O'Brien CD,Lim P,Sun J,Albelda SM

    更新日期：2003-04-01 00:00:00

  • Platelet membrane microparticles in blood bank fresh frozen plasma and cryoprecipitate.

    abstract：:Cryoprecipitate has been demonstrated to correct the bleeding abnormality of patients with some congenital (storage pool disease) and acquired (uremia) platelet abnormalities, but the reason for this effect is unknown. We found significant platelet contamination in plasma harvested to prepare fresh frozen plasma and c...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： George JN,Pickett EB,Heinz R

    更新日期：1986-07-01 00:00:00

  • A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivo.

    abstract：:We have developed a new helper-dependent (HD) adenoviral vector FTC that contains 3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA, matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To determine the most robust human coagulation factor IX (hFIX) expression casse...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.v99.11.3923

    authors： Ehrhardt A,Kay MA

    更新日期：2002-06-01 00:00:00