The EMT regulator ZEB2 is a novel dependency of human and murine acute myeloid leukemia.

Abstract:

:Acute myeloid leukemia (AML) is a heterogeneous disease with complex molecular pathophysiology. To systematically characterize AML's genetic dependencies, we conducted genome-scale short hairpin RNA screens in 17 AML cell lines and analyzed dependencies relative to parallel screens in 199 cell lines of other cancer types. We identified 353 genes specifically required for AML cell proliferation. To validate the in vivo relevance of genetic dependencies observed in human cell lines, we performed a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein. Integrating the results of these interference RNA screens and additional gene expression data, we identified the transcription factor ZEB2 as a novel AML dependency. ZEB2 depletion impaired the proliferation of both human and mouse AML cells and resulted in aberrant differentiation of human AML cells. Mechanistically, we showed that ZEB2 transcriptionally represses genes that regulate myeloid differentiation, including genes involved in cell adhesion and migration. In addition, we found that epigenetic silencing of the miR-200 family microRNAs affects ZEB2 expression. Our results extend the role of ZEB2 beyond regulating epithelial-mesenchymal transition (EMT) and establish ZEB2 as a novel regulator of AML proliferation and differentiation.

journal_name

Blood

journal_title

Blood

authors

Li H,Mar BG,Zhang H,Puram RV,Vazquez F,Weir BA,Hahn WC,Ebert B,Pellman D

doi

10.1182/blood-2016-05-714493

subject

Has Abstract

pub_date

2017-01-26 00:00:00

pages

497-508

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2016-05-714493

journal_volume

129

pub_type

杂志文章

相关文献

BLOOD文献大全
  • The rhesus macaque as an animal model for hemophilia B gene therapy.

    abstract::We have determined the 2905 nucleotide sequence of the rhesus macaque factor IX complementary DNA (cDNA) and found it to be greater than 95% identical to that of the human factor IX cDNA. The cDNA has a large 3' untranslated region like the human cDNA, but unlike the human cDNA has two polyadenylation sites 224 nucleo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lozier JN,Metzger ME,Donahue RE,Morgan RA

    更新日期:1999-03-15 00:00:00

  • Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes.

    abstract::T cells are known to interact cooperatively with monocytes to produce Colony-Stimulating Factors (CSF), although T cell-mediated signals leading to CSF secretion by monocytes are not completely understood. We have made use of Northern blot hybridization and specific bioassays to study the effects of the T cell product...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wieser M,Bonifer R,Oster W,Lindemann A,Mertelsmann R,Herrmann F

    更新日期:1989-04-01 00:00:00

  • In vivo removal of malaria parasites from red blood cells without their destruction in acute falciparum malaria.

    abstract::During acute falciparum malaria infection, red blood cells (RBC) containing abundant ring-infected erythrocyte surface antigen (Pf 155 or RESA), but no intracellular parasites, are present in the circulation. These RESA-positive parasite negative RBC are not seen in parasite cultures in vitro. This indicates that in a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Angus BJ,Chotivanich K,Udomsangpetch R,White NJ

    更新日期:1997-09-01 00:00:00

  • Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma.

    abstract::Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gribben JG,Neuberg D,Freedman AS,Gimmi CD,Pesek KW,Barber M,Saporito L,Woo SD,Coral F,Spector N

    更新日期:1993-06-15 00:00:00

  • A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis.

    abstract::The kidney is involved in 70% of patients with immunoglobulin light-chain (AL) amyloidosis, but little is known on progression or reversibility of renal involvement, and criteria for renal response have never been validated. Newly diagnosed patients from the Pavia (n = 461, testing cohort) and Heidelberg (n = 271, val...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-04-570010

    authors: Palladini G,Hegenbart U,Milani P,Kimmich C,Foli A,Ho AD,Vidus Rosin M,Albertini R,Moratti R,Merlini G,Schönland S

    更新日期:2014-10-09 00:00:00

  • HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients.

    abstract::Human immunodeficiency virus (HIV) infection is characterized by the massive infiltration of secondary lymphoid organs with activated CD8(+) T lymphocytes. While converging data indicated that these cells were HIV-specific cytotoxic T lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was lackin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.9.2695

    authors: Hosmalin A,Samri A,Dumaurier MJ,Dudoit Y,Oksenhendler E,Karmochkine M,Autran B,Wain-Hobson S,Cheynier R

    更新日期:2001-05-01 00:00:00

  • Regulation of vascular endothelial growth factor receptor 2 trafficking and angiogenesis by Golgi localized t-SNARE syntaxin 6.

    abstract::Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in physiologic and pathologic angiogenesis. Plasma membrane (PM) levels of VEGFR2 are regulated by endocytosis and secretory transport through the Golgi apparatus. To date, the mechanism whereby the VEGFR2 traffics through the Golgi apparatus rema...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-06-291690

    authors: Manickam V,Tiwari A,Jung JJ,Bhattacharya R,Goel A,Mukhopadhyay D,Choudhury A

    更新日期:2011-01-27 00:00:00

  • Altered factor VII activity in hemophilia.

    abstract::Factor VII levels have been studied in hemophilia A and B plasmas and normal controls in a controlled, prospective study. Three assay methods were used: a standard clotting assay (FVIIc-A); a modified clotting assay (FVIIc-B) (Seligsohn et al, Blood 52:978-988, 1978); and a coupled amidolytic assay. By the FVIIc-B ass...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miller BC,Hultin MB,Jesty J

    更新日期:1985-04-01 00:00:00

  • Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis.

    abstract::Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. β-Galactosidase staining in PRCP(gt/gt) mice reveals expression in kidney and vasculature. Invasive telemetric moni...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-11-318527

    authors: Adams GN,LaRusch GA,Stavrou E,Zhou Y,Nieman MT,Jacobs GH,Cui Y,Lu Y,Jain MK,Mahdi F,Shariat-Madar Z,Okada Y,D'Alecy LG,Schmaier AH

    更新日期:2011-04-07 00:00:00

  • CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

    abstract::CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-03-768507

    authors: Bai M,Grieshaber-Bouyer R,Wang J,Schmider AB,Wilson ZS,Zeng L,Halyabar O,Godin MD,Nguyen HN,Levescot A,Cunin P,Lefort CT,Soberman RJ,Nigrovic PA

    更新日期:2017-11-09 00:00:00

  • Negative effects of GM-CSF signaling in a murine model of t(8;21)-induced leukemia.

    abstract::The t(8;21)(q22;q22) is common in adult acute myeloid leukemia (AML). The RUNX1-ETO fusion protein that is expressed by this translocation is poorly leukemogenic and requires additional mutations for transformation. Loss of sex chromosome (LOS) is frequently observed in t(8;21) AML. In the present study, to evaluate w...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-04-350694

    authors: Matsuura S,Yan M,Lo MC,Ahn EY,Weng S,Dangoor D,Matin M,Higashi T,Feng GS,Zhang DE

    更新日期:2012-03-29 00:00:00

  • Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation.

    abstract::Severe congenital neutropenia (CN) (Kostmann syndrome) is a hematologic disorder characterized by a maturation arrest of myelopoiesis at the promyelocyte/myelocyte stage of development. This arrest results in severe neutropenia leading to absolute neutrophil counts (ANC) below 0.2 x 10(9)/L associated with severe bact...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Zeidler C,Welte K,Barak Y,Barriga F,Bolyard AA,Boxer L,Cornu G,Cowan MJ,Dale DC,Flood T,Freedman M,Gadner H,Mandel H,O'Reilly RJ,Ramenghi U,Reiter A,Skinner R,Vermylen C,Levine JE

    更新日期:2000-02-15 00:00:00

  • Culture of human fetal B-cell precursors on bone marrow stroma maintains highly proliferative CD20dim cells.

    abstract::Growth of human B-cell precursors (BCP) was achieved by plating fetal CD10+ surface-mu (s mu)- cells in liquid medium onto bone marrow-derived fibroblastic stromal cell layers deprived of hematopoietic cells. Proliferation of the fetal BCP was strongly potentiated by the addition of interleukin-7 (IL-7) to the culture...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Moreau I,Duvert V,Banchereau J,Saeland S

    更新日期:1993-03-01 00:00:00

  • Notes from the Director, National Heart, Lung, and Blood Institute: transitions.

    abstract::During this time of transition in the federal government and the National Institutes of Health, I write to assure the Blood community of the National Heart, Lung, and Blood Institute's (NHLBI) commitment to new and established investigators as outlined in the NHLBI Strategic Plan. This perspective discusses the NHLBI ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-12-194100

    authors: Nabel EG

    更新日期:2009-03-26 00:00:00

  • Large granular lymphocyte proliferation: an analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents.

    abstract::The status of the T cell receptor beta and gamma genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T alpha and complete T beta gene transcripts were not detected, but a 1.0-kilobase T beta gene tran...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chan WC,Dahl C,Waldmann T,Link S,Mawle A,Nicholson J,Bach FH,Bongiovanni K,McCue PA,Winton EF

    更新日期:1988-01-01 00:00:00

  • Thrombopoietic effects and toxicity of interleukin-6 in patients with ovarian cancer before and after chemotherapy: a multicentric placebo-controlled, randomized phase Ib study.

    abstract::Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in normal and sublethally irradiated mice, dogs, and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carcinoma. IL-6 was administered during an ...

    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: D'Hondt V,Humblet Y,Guillaume T,Baatout S,Chatelain C,Berlière M,Longueville J,Feyens AM,de Greve J,Van Oosterom A

    更新日期:1995-05-01 00:00:00

  • Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors.

    abstract::To assess a possible role in tumor progression, the occurrence and type of K- and N-RAS mutations were determined in purified tumor cells, including samples from patients with premalignant monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and extramedullary plasma cell (PC) tumors (ExPC...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-03-0833

    authors: Rasmussen T,Kuehl M,Lodahl M,Johnsen HE,Dahl IM

    更新日期:2005-01-01 00:00:00

  • Enrichment and functional characterization of Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ bone marrow cells from mice with an Ly-6a haplotype.

    abstract::Approximately 4% to 5% of all bone marrow (BM) cells and 8% to 9% of low density BM cells from FVB/N and BALB/c mice (Ly-6a haplotype) show high to intermediate expression of Ly-6E.1 antigen, recognized by the Sca-1 antibody. Functional properties of enriched cells expressing Ly-6E.1-allelic form of Sca-1 antigen were...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Jurecic R,Van NT,Belmont JW

    更新日期:1993-11-01 00:00:00

  • The current state of sickle cell trait: implications for reproductive and genetic counseling.

    abstract::Sickle cell trait (SCT) is unique among the carrier states that are identified during newborn screening. Unlike other heterozygous states for rare recessive diseases, SCT is exceedingly prevalent throughout regions of the world, making sickle cell disease one of the most common monogenetic diseases worldwide. Because ...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2018-06-848705

    authors: Pecker LH,Naik RP

    更新日期:2018-11-29 00:00:00

  • Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells.

    abstract::Myeloma plasma cells constitute 10% to 90% of the total bone marrow cell count in patients with multiple myeloma (MM). These cells express a variety of cell surface markers, such as HLA-ABC and HLA-DR, and surface antigens that are necessary for professional antigen-presenting cells, including adhesion and costimulato...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yi Q,Dabadghao S,Osterborg A,Bergenbrant S,Holm G

    更新日期:1997-09-01 00:00:00

  • Cytogenetic evolution patterns in non-Hodgkin's lymphoma.

    abstract::Secondary chromosomal aberrations were surveyed in non-Hodgkin's lymphomas (NHL) reported in the literature with one of the following, presently recognized, primary abnormalities: t(2;5), +3, t(3;14), del(6q), +X, and -Y. Of 2,175 NHLs with clonal karyotypic changes, 908 (42%) had one of the 13 selected primary chromo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Johansson B,Mertens F,Mitelman F

    更新日期:1995-11-15 00:00:00

  • Widespread and dynamic translational control of red blood cell development.

    abstract::Cell development requires tight yet dynamic control of protein production. Here, we use parallel RNA and ribosome profiling to study translational regulatory dynamics during murine terminal erythropoiesis. Our results uncover pervasive translational control of protein synthesis, with widespread alternative translation...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-09-741835

    authors: Alvarez-Dominguez JR,Zhang X,Hu W

    更新日期:2017-02-02 00:00:00

  • Exploring the "minimal" structure of a functional ADAMTS13 by mutagenesis and small-angle X-ray scattering.

    abstract::Human ADAMTS13 is a multidomain protein with metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains, followed by 7 additional T domains and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. ADAMTS13 inhibits the ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2018-11-886309

    authors: Zhu J,Muia J,Gupta G,Westfield LA,Vanhoorelbeke K,Tolia NH,Sadler JE

    更新日期:2019-04-25 00:00:00

  • Reversal of in situ T-cell exhaustion during effective human antileukemia responses to donor lymphocyte infusion.

    abstract::Increasing evidence across malignancies suggests that infiltrating T cells at the site of disease are crucial to tumor control. We hypothesized that marrow-infiltrating immune populations play a critical role in response to donor lymphocyte infusion (DLI), an established and potentially curative immune therapy whose p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-08-523001

    authors: Bachireddy P,Hainz U,Rooney M,Pozdnyakova O,Aldridge J,Zhang W,Liao X,Hodi FS,O'Connell K,Haining WN,Goldstein NR,Canning CM,Soiffer RJ,Ritz J,Hacohen N,Alyea EP 3rd,Kim HT,Wu CJ

    更新日期:2014-02-27 00:00:00

  • The inherited diseases of hemoglobin are an emerging global health burden.

    abstract::It is estimated that in excess of 300,000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries. As these countries go through an epidemiologic transition, with a reduction in childhood and infant mortality due to ...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2010-01-251348

    authors: Weatherall DJ

    更新日期:2010-06-03 00:00:00

  • Immunocytochemical localization of fibrinogen on washed human platelets. Lack of requirement for fibrinogen during adenosine diphosphate-induced responses and enhanced fibrinogen binding in a medium with low calcium levels.

    abstract::The association of fibrinogen with washed human platelets was examined by immunocytochemistry during aggregation induced by adenosine diphosphate (ADP) and during deaggregation. The platelets were suspended either in a medium containing 2 mmol/L Ca2+ or in a medium containing no added Ca2+ (20 mumol/L Ca2+). Platelets...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Suzuki H,Kinlough-Rathbone RL,Packham MA,Tanoue K,Yamazaki H,Mustard JF

    更新日期:1988-04-01 00:00:00

  • Domain 5 of high molecular weight kininogen (kininostatin) down-regulates endothelial cell proliferation and migration and inhibits angiogenesis.

    abstract::We have demonstrated that high molecular weight kininogen (HK) binds specifically on endothelial cells to domain 2/3 of the urokinase receptor (uPAR). Inhibition by vitronectin suggests that kallikrein-cleaved HK (HKa) is antiadhesive. Plasma kallikrein bound to HK cleaves prourokinase to urokinase, initiating cell-as...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Colman RW,Jameson BA,Lin Y,Johnson D,Mousa SA

    更新日期:2000-01-15 00:00:00

  • Trafficking of the major virulence factor to the surface of transfected P. falciparum-infected erythrocytes.

    abstract::After invading human red blood cells (RBCs) the malaria parasite Plasmodium falciparum remodels the host cell by trafficking proteins to the RBC compartment. The virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) is responsible for cytoadherence of infected cells to host endothelial receptors. Thi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-12-4666

    authors: Knuepfer E,Rug M,Klonis N,Tilley L,Cowman AF

    更新日期:2005-05-15 00:00:00

  • Expression of human inducible nitric oxide synthase gene in T-cell lines infected with human T-cell leukemia virus type-I and primary adult T-cell leukemia cells.

    abstract::We examined the expression of messenger RNA (mRNA) of the human inducible nitric oxide synthase (hiNOS) gene in a panel of human T-cell lines. Reverse transcriptase-polymerase chain reaction showed that human T-cell leukemia virus type-I (HTLV-I)-infected T-cell lines (MT-1, SLB-1, and C5/MJ) expressed mRNA for the hi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Mori N,Nunokawa Y,Yamada Y,Ikeda S,Tomonaga M,Yamamoto N

    更新日期:1999-10-15 00:00:00

  • Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination.

    abstract::Naive and memory CD8(+) T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8(+) T cells...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-12-192419

    authors: Klebanoff CA,Yu Z,Hwang LN,Palmer DC,Gattinoni L,Restifo NP

    更新日期:2009-08-27 00:00:00