346c895f64892025acde4207c9899f52 pmc_27297662.pdf a329ee6dad2728a37919dfa48f1b9a5a467d835b pmc_27297662.pdf Title: Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics Subject: Nature Communications 7, (2016). doi:10.1038/ncomms11889 Author: Eloy F. Robles Creator: Arbortext Advanced Print Publisher 9.0.226/W Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Fri Jun 3 14:26:07 2016 CEST ModDate: Tue Jun 7 15:44:06 2016 CEST Tagged: no UserProperties: no Suspects: no Form: AcroForm JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 782.362 pts Page rot: 0 File size: 4521456 bytes Optimized: yes PDF version: 1.6 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OBGHBF+AdvOTea1a7398 Type 1C Custom yes yes yes 541 0 OBGHBG+AdvEls-ent2 Type 1C WinAnsi yes yes no 542 0 OBGHCH+AdvOT9bd21c25.I Type 1C Custom yes yes yes 550 0 OBGHCI+AdvPi1 Type 1C WinAnsi yes yes no 551 0 OBGHCJ+AdvOTcb88df00 Type 1C Custom yes yes yes 558 0 OBGHGI+Arial-BoldMT Type 1C WinAnsi yes yes no 559 0 OBGHJI+AdvOTf23bb480 Type 1C Custom yes yes yes 560 0 OBGIBG+AdvTTda6f6cb8.B Type 1C Custom yes yes yes 569 0 OBGIHI+AdvOT7d6df7ab.I Type 1C Custom yes yes yes 288 0 OBGIIJ+AdvOT45bf69de.BI Type 1C Custom yes yes yes 301 0 OBGIIK+AdvOTb65e897d.B Type 1C Custom yes yes yes 302 0 OBGIJK+AdvPi2 Type 1C WinAnsi yes yes no 297 0 OBGIHF+AdvOT125c650c Type 1C Custom yes yes yes 282 0 OBGIHG+AdvOT1ef757c0 Type 1C Custom yes yes yes 289 0 OBGIHH+AdvP4C4E74 Type 1C Custom yes yes yes 290 0 OBIEMO+Helvetica-Bold Type 1C WinAnsi yes yes no 318 0 OBIENP+Helvetica Type 1C WinAnsi yes yes no 315 0 OBIEOP+Helvetica-Oblique Type 1C WinAnsi yes yes no 308 0 OBIEPA+Symbol Type 1C Custom yes yes yes 323 0 OBILLI+AdvOTe75a9404.I Type 1C Custom yes yes yes 312 0 OBMIKC+AdvGreek_B Type 1C WinAnsi yes yes no 329 0 OBMIKD+AdvEls-ent4 Type 1C WinAnsi yes yes no 325 0 OCCKCN+AdvItcSymbol-M Type 1C WinAnsi yes yes no 339 0 OCGPNC+AdvEls-ent7 Type 1C WinAnsi yes yes no 348 0 OCGPPC+Advsymbol Type 1C Custom yes yes no 349 0 Jhove (Rel. 1.6, 2011-01-04) Date: 2019-02-14 18:45:11 CET RepresentationInformation: pmc_27297662.pdf ReportingModule: PDF-hul, Rel. 1.8 (2009-05-22) LastModified: 2018-02-06 08:59:33 CET Size: 4521456 Format: PDF Version: 1.6 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 595 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: title_link Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7c53a9eb Children: Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed17bee Children: Item: Title: NKX2-3 expression in marginal-zone B- cell &!QJ;lymphomas Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2a33fae0 Item: Title: Characterization of NKX2-3 deficiency in B cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@707f7052 Item: Title: NKX2-3 promotes expansion of splenic marginal-zone B cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11028347 Item: Title: Figure™1NKX2-3 expression is deregulated in marginal-zone B- cell lymphomas.(a) Partial G- banded karyotype showing a t(10;14)(q24;q32) translocation in a patient with SMZL (case 1). Arrows mark the derivative chromosomes 10 and 14. (b,d) Interphase FISH Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@14899482 Item: Title: Figure™2Nkx2-3-sol- and Emgr-NKX2-3 transgenic (TG) mice show abnormal lymphopoiesis.(a) Murine Nkx2-3 expression measured by quantitative RT-PCR in haematopoietic cell subpopulations isolated from healthy C57BLsol6 mice. Haematopoietic stem cells (HSC, l Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@21588809 Children: Item: Title: Emgr-NKX2-3 mice develop human-like marginal-zone lymphomas Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2aae9190 Item: Title: NKX2-3 induces constitutive BCR signalling in young mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2f333739 Item: Title: Figure™3Emgr-NKX2-3 mice develop human-like marginal-zone lymphomas.(a) Kaplan-Meier overall survival curves for the two Emgr-NKX2-3 transgenic lines and WT mice. (b) Haematoxilin-eosin (H&E) staining of formalin-fixed paraffin-embedded spleen tissues of Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77468bd9 Children: Item: Title: NKX2-3 regulates B cells dynamics in lymphoid tissues Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12bb4df8 Item: Title: Figure™4NKX2-3 induces B- cell receptor signalling in B cells from young mice.(a) Cell survival of in™vitro cell cultures containing isolated CD19+ cells from WT and transgenic (TG) mice. Data from three experiments are shown. (b) BrdU staining of WT and Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4cc77c2e Children: Item: Title: NKX2-3-expressing B cells are sensitive to BCR blockade Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a7b0070 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@39a054a5 Item: Title: Figure™5NKX2-3 induces activation of BCR and downstream signalling pathways in mouse B- cell lymphomas.(a) Western blot analysis showed increase in AKT phosphorylation levels in splenic CD19+ cells isolated from 18-month-old transgenic (TG) mice in compar Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@71bc1ae4 Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6ed3ef1 Children: Item: Title: Human primary samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2437c6dc Item: Title: Long-distance inverse PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1f89ab83 Item: Title: Quantitative real-time PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e73f9ac Item: Title: Figure™6Phenotypic analysis and characterization of cell dynamics in NKX2-3-expressing B cells.(a) Representative flow cytometry profiles (grey filled histogram) of forward side scatter (FSC) and the indicated molecules at the surface of WT B cells and NK Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@61064425 Item: Title: Figure™7Functional characterization of cell dynamic changes in Emgr-NKX2-3 transgenic mice.(a) Migration frequencies of transgenic B cells non-treated (none) or treated with the indicated chemical inhibitors (AMD, CXCR4 antagonist, 10thinspmgrM; A286, LFA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b1d7fff Children: Item: Title: Fluorescence in™situ hybridization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@299a06ac Item: Title: Generation of NKX2-3 mAb Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@383534aa Item: Title: IHC and western blot analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6bc168e5 Item: Title: Generation and characterization of NKX2-3-deficient mice and Emgr-NKX2-3 transgenic mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b3300e5 Item: Title: Mouse blood cell count Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2e5c649 Item: Title: Measurement of spleen size using ultrasounds Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@136432db Item: Title: Flow cytometry analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7382f612 Item: Title: Cell isolation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1055e4af Item: Title: Cell survival and proliferation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3caeaf62 Item: Title: V(D)J Recombination analysis of mouse B- cell tumours Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e6ea0c6 Item: Title: Gene expression microarray data analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a38e57f Item: Title: Functional and pathway analysis of gene expression signatures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5577140b Item: Title: High-resolution comparative genomic hybridization (aCGH) to microarray Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1c6b6478 Item: Title: Chemotaxis assays Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@67f89fa3 Item: Title: Calcium mobilization assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4ac68d3e Item: Title: Adhesion assays and time-lapse microscopy on planar lipid bilayers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@277c0f21 Item: Title: IF studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6073f712 Item: Title: Chemical inhibitors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@43556938 Item: Title: Electrophoretic mobility gel shift array Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3d04a311 Item: Title: Statistical analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a46a697 Item: Title: McGinnisW.KrumlaufR.Homeobox genes and axial patterningCell682833021992Garcia-FernandezJ.The genesis and evolution of homeobox gene clustersNat. Rev. Genet.68818922005BibenC.WangC. C.HarveyR. P.NK-2 class homeobox genes and pharyngealsoloral patterning: N Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5f205aa Item: Title: We thank Jerry Adams (WEHI, Melbourne, Australia) for providing the pEmgrSR vector, Vincent Dubus (Genoway, Lyon, France) for support during transgenic mouse generation, Carlos Ortiz de Solorzano (CIMA, Pamplona, Spain) for spleen ultrasound studies in mi Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6d86b085 Item: Title: ACKNOWLEDGEMENTS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@75828a0f Item: Title: Author contributions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3abfe836 Item: Title: Additional information Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2ff5659e Info: Title: Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics Author: Eloy F. 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-225, 1000, 931 FontFile3: true Encoding: WinAnsiEncoding Font: BaseFont: OBIEMO+Helvetica-Bold FontSubset: true FirstChar: 97 LastChar: 105 FontDescriptor: FontName: OBIEMO+Helvetica-Bold Flags: Nonsymbolic, ForceBold FontBBox: -170, -228, 1003, 962 FontFile3: true Encoding: WinAnsiEncoding XMP: application/pdf doi:10.1038/ncomms11889 Eloy F. Robles Maria Mena-Varas Laura Barrio Sara V. Merino-Cortes Péter Balogh Ming-Qing Du Takashi Akasaka Anton Parker Sergio Roa Carlos Panizo Idoia Martin-Guerrero Reiner Siebert Victor Segura Xabier Agirre Laura Macri-Pellizeri Beatriz Aldaz Amaia Vilas-Zornoza Shaowei Zhang Sarah Moody Maria Jose Calasanz Thomas Tousseyn Cyril Broccardo Pierre Brousset Elena Campos-Sanchez Cesar Cobaleda Isidro Sanchez-Garcia Jose Luis Fernandez-Luna Ricardo Garcia-Muñoz Esther Pena Beatriz Bellosillo Antonio Salar Maria Joao Baptista Jesús Maria Hernandez-Rivas Marcos Gonzalez Maria Jose Terol Joan Climent Antonio Ferrandez Xavier Sagaert Ari M. Melnick Felipe Prosper David G. Oscier Yolanda R. Carrasco Martin J. S. Dyer Jose A. Martinez-Climent Nature Communications 7, (2016). doi:10.1038/ncomms11889 Nature Publishing Group © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics Acrobat Distiller 8.1.0 (Windows) © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. 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