Holdings: The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia

The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia:

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Bibliographic Details
Main Author:	Wang, Fan (Author)
Format:	Thesis Book
Language:	English
Published:	Ulm 2018
Subjects:	Forkhead transcription factors. Precursor cell lymphoblastic leukemia-lymphoma. Hochschulschrift
Online Access:	Inhaltsverzeichnis Inhaltsverzeichnis
Physical Description:	XIII, 94 Blätter Illustrationen, Diagramme 30 cm

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MARC


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adam_text	TABLE OF CONTENTS ABBREVIATIONS............................................................................................................... VI 1. INTRODUCTION................................................................................................................1 1.1 FOXO TRANSCRIPTION FACTORS ................................................................................ 1 1.1.1 FOXOS EXPRESSION AND FUNCTIONS...............................................................2 1.1.2 TARGET GENES OF FO XO S...............................................................................3 1.1.3 POSTTRANSLATIONAL REGULATION OF FOXOS.......................................................3 1.2 B CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (BOP-ALL) ......................... 8 1.2.1 EARLY B-CELL DEVELOPMENT..............................................................................8 1.2.2 BOP-ALL.......................................................................................................11 1.2.3 THE ROLE OF F0X01 IN EARLY STAGES OF B CELL DEVELOPM ENT .................... 12 1.2.4 ROLE OF F0X01 IN BOP-ALL ....................................................................... 12 1.3 C C N D 3.................................................................................................................13 1.4 AIMS OF THE STUDY.............................................................................................. 15 2. MATERIAL AND METHODS.............................................................................................17 2.1 M ATERIALS.............................................................................................................. 17 2.1.1 REAGENTS AND CHEM ICALS.............................................................................17 2.1.2 K ITS ................................................................................................................ 18 2.1.3 VECTORS.......................................................................................................... 18 2.1.4 ANTIBODIES......................................................................................................19 2.1.5 PLASTIC W A RE .................................................................................................. 19 2.1.6 LABORATORY EQUIPMENT .... . ............................................................................ 20 2.1.7 SOFTWARES..................................................................................... 20 2.1.8 MISCELLANEOUS...............................................................................................20 2.2 MOLECULAR BIOLOGICAL METHODS............................................................................ 21 2.2.1 CLONING CONSTRUCTS....................................................................................... 21 2.2.2 CLONING PROCEDURE....................................................................................... 25 2.3 CELL CULTURE METHODS...........................................................................................26 2.3.1 CELL LINES AND CULTURE CONDITIONS.................................................................26 2.3.2 STR ANALYSIS AND MYCOPLASMA DETECTION ................................................. 27 2.3.3 CELL TREATM ENTS............................................................................................. 27 2.4 TRANSFECTION.........................................................................................................28 2.5 LENTIVIRAL TRANSDUCTION.........................................................................................29 2.6 CELL VIABILITY ANALYSIS...........................................................................................30 2.7 MTT ASSAY...........................................................................................................30 2.8 CELL CYCLE AND APOPTOSIS ANALYSIS..................................................................... 31 2.9 FLOW CYTOMETRY AND CELL SORTING ......................................................................... 31 2.10 IMMUNOFLUORESCENCE.........................................................................................32 2.11 ANALYSIS OF NUCLEIC ACIDS.................................................................................. 32 2.12 DIRECT SEQUENCING.............................................................................................33 2.13 GENE EXPRESSION PROFILING (GEP) AND GENE SET ENRICHMENT ANALYSIS (GSEA) 34 2.15 PROTEIN BIOCHEMICAL METHODS .......................................................................... 34 2.16 STATISTICAL ANALYSIS.............................................................................................37 3. RESULTS....................................................................................................................38 3.1 F0X01 IS EXPRESSED IN BCP-ALL.....................................................................38 3.2 OVEREXPRESSION OF F0X01 CAN INHIBIT THE BCP-ALL CELL GROWTH ................... 42 3.3 CONSTITUTIVELY ACTIVATED AKT STRONGLY INHIBITS THE CELL GROWTH OF BCP-ALL...44 3.4 F0X01 KNOCKDOWN ABOROGATES THE PROLIFERATION OF BCP-ALL CE LLS ............. 45 3.5 THE CYTOTOXIC EFFECT OF F0X01 SHRNA CAN BE RESCUED BY OVEREXPRESSION OF W TF O X O I................................................................................................................... 47 3.6 F 0 X 0 3 KNOCKDOWN SLIGHTLY INHIBITS THE BCP-ALL CELL GROWTH ....................... 48 3.7 F0X01 KNOCKDOWN INDUCES G0/G1 CELL CYCLE ARREST AND APOPTOSIS IN BCP- ALL ............................................................................................................................. 49 3.8 F0X01 KNOCKDOWN SUPPRESSES CCND3 RELATED CELL SURVIVAL ....................... 50 3.9 CCND3 OVEREXPRESSION RESCUES BCP-ALL CELLS AGAINST THE CYTOTOXITY INDUCED BY F0X01 REPRESSION................................................................................. 53 3.10 F0X01 KNOCKDOWN DOWNREGULATES MYC EXPRESSION AND MTORCI ACTIVITY 54 3.11 BCP-ALL CELL LINES ARE HIGHLY SENSITIVE TO THE F0X01 INHIBITOR AS1842856 57 3.12 AS1842856 INHIBITED THE CELL GROWTH OF BCP-ALL CELL BY INDUCING APOPTOSIS AND 60/61 CELL CYCLE ARREST.......................................................................................59 3.14 AS1842856 CYTOTOXICITY DEPENDS ON F0X01 INHIBITION ................................... 61 3.15 AS 1842856 INHIBITS F0X01 TARGET GENES BY USING 6 E P ...............................62 3.16 CCND3 OVEREXPRESSION PROTECTS BCP-ALL CELL LINES FROM THE CYTOTOXIC EFFECT OF AS 1842856................................................................................................. 66 3.17 AS1842856 INHIBITS MTORCS ACTIVITY IN BCP-ALL C E LLS ............................... 69 4. DISCUSSION............................................................................................................... 71 5. REFERENCES............................................................................................................... 79 6. STATUTORY DECLARATION.............................................................................................93 7. ACKNOWLEDGMENTS.................................................................................................. 94
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spelling	Wang, Fan Verfasser (DE-588)116450276X aut The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia submitted by Fan Wang Ulm 2018 XIII, 94 Blätter Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Universität Ulm 2018 Forkhead transcription factors. Precursor cell lymphoblastic leukemia-lymphoma. (DE-588)4113937-9 Hochschulschrift gnd-content Universität Ulm (DE-588)30607-1 dgg B:DE-101 application/pdf http://d-nb.info/1165176718/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030926942&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle	Wang, Fan The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia
subject_GND	(DE-588)4113937-9
title	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia
title_auth	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia
title_exact_search	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia
title_full	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia submitted by Fan Wang
title_fullStr	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia submitted by Fan Wang
title_full_unstemmed	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia submitted by Fan Wang
title_short	The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia
title_sort	the role of foxo1 in b cell precursor acute lymphoblastic leukemia
topic_facet	Hochschulschrift
url	http://d-nb.info/1165176718/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030926942&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
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