The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia:
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| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Ulm
2018
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| Beschreibung: | XIII, 94 Blätter Illustrationen, Diagramme 30 cm |
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| 245 | 1 | 0 | |a The role of FOXO1 in B-cell precursor acute lymphoblastic leukemia |c submitted by Fan Wang |
| 264 | 1 | |a Ulm |c 2018 | |
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| 502 | |b Dissertation |c Universität Ulm |d 2018 | ||
| 653 | |a Forkhead transcription factors. | ||
| 653 | |a Precursor cell lymphoblastic leukemia-lymphoma. | ||
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Datensatz im Suchindex
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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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| author | Wang, Fan |
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| discipline | Chemie / Pharmazie |
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| physical | XIII, 94 Blätter Illustrationen, Diagramme 30 cm |
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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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