Deregulated circular RNA expression in acute myeloid leukemia (AML):
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| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Ulm
2019
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | xix, 172 Blätter Illustrationen, Diagramme 30 cm |
Internformat
MARC
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| 100 | 1 | |a Lux, Susanne |e Verfasser |0 (DE-588)1192995805 |4 aut | |
| 245 | 1 | 0 | |a Deregulated circular RNA expression in acute myeloid leukemia (AML) |c Susanne Julia Andrea Lux née Hirsch |
| 264 | 1 | |a Ulm |c 2019 | |
| 300 | |a xix, 172 Blätter |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Ulm University |d 2018 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1193596416/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031648665&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-031648665 | ||
Datensatz im Suchindex
| _version_ | 1804180714161176576 |
|---|---|
| adam_text | CONTENTS
LIST
OF
FIGURES
X
LIST
OF
TABLES
XI
LIST
OF
ABBREVIATIONS
XII
1
INTRODUCTION
1
1.1
ACUTE
MYELOID
LEUKEMIA
............................................................................
1
1.2
AML
WITH
NPM1
MUTATIONS
......................................................................
2
1.2.1
NPM1
FUNCTIONS
............................................................................
3
1.2.2
CIRCULAR
AND
LINEAR
NPM1
SPLICE
VARIANTS
..................................
4
1.3
CORE
BINDING
FACTOR
LEUKEMIA
................................................................
6
1.3.1
INHIBITION
OF
CBF-MEDIATED
TRANSCRIPTION
BY
THE
FUSION
PROTEINS
6
1.4
AML
WITH
SPLICING
FACTOR
MUTATIONS
..........................................................
7
1.4.1
U2AF1
..............................................................................................
8
1.4.2
SF3B1
..............................................................................................
8
1.4.3
SRSF2
...........................................................................................
10
1.5
ALTERNATIVE
AND
ABERRANT
SPLICING
IN
HEMATOLOGIC
MALIGNANCIES
....
10
1.6
NON-CODING
RNAS
IN
CANCER
AND
HEMATOLOGIC
MALIGNANCIES
...............
11
1.7
CIRCULAR
RNAS
...........................................................................................
13
1.8
CIRCULAR
RNAS
IN
CANCER
...........................................................................
19
1.8.1
THE
ROLE
OF
CIRCRNAS
IN
THE
PATHOLOGY
OF
HEMATOLOGIC
MALIG
NANCIES
...........................................................................................
19
1.8.2
THE
ROLE
OF
CIRCRNAS
IN
THE
PATHOLOGY
OF
SOLID
TUMORS
................
20
IV
1.9
PROJECT
AIMS
.................................................................................................
31
2
MATERIALS
AND
METHODS
32
2.1
MATERIALS
........................................................................................................
32
2.1.1
CHEMICALS
AND
REAGENTS
................................................................
32
2.1.2
KITS
.....................................................................................................
35
2.1.3
LABORATORY
EQUIPMENT
......................................................................
36
2.1.4
PLASTIC
WARE
.....................................................................................
38
2.1.5
SOFTWARE
...........................................................................................
39
2.1.6
MEDIA
AND
BUFFERS
............................................................................
40
2.1.7
PRIMERS
..............................................................................................
41
2.1.8
VECTORS
..............................................................................................
44
2.1.9
CELL
LINES
...........................................................................................
44
2.1.10
PATIENT
MATERIAL
AND
HEALTHY
CONTROL
SAMPLES
................................
45
2.2
METHODS
...........................................................................................................
46
2.2.1
RNA
ISOLATION
AND
QUALITY
CONTROL
.................................................
46
2.2.2
REVERSE
TRANSCRIPTION
......................................................................
47
2.2.3
POLYMERASE
CHAIN
REACTION
(PGR)
.................................................
48
2.2.4
AGAROSE
GEL
ELECTROPHORESIS
..........................................................
49
2.2.5
RNA-SEQ
LIBRARY
PREPARATION
AND
SEQUENCING
............................
49
2.2.6
CIRCULAR
RNA
ANALYSIS
PIPELINE
.......................................................
50
2.2.7
MOLECULAR
SIGNATURE
ANALYSIS
AND
GENE
SET
ENRICHMENT
ANALYSIS
51
2.2.8
OXFORD
NANOPORE
SEQUENCING
..........................................................
52
2.2.9
CLONING
OF
OLIGOS
FOR
SHRNA
CONSTRUCTS
........................................
54
2.2.10
TRANSFECTION
OF
HEK293T
CELLS
FOR
LENTIVIRUS
PRODUCTION
...
57
2.2.11
TRANSDUCTION
OF
OCI-AML5
CELLS
....................................................
58
2.2.12
VIABLE
CELL
COUNT
USING
THE
TRYPAN
BLUE
EXCLUSION
METHOD
..
59
2.2.13
APOPTOSIS
ASSAY
...............................................................................
59
2.2.14
CYTOSPIN
...............................................................................................
60
2.2.15
PROTEIN
LYSATE
PREPARATION
.............................................................
60
2.2.16
PROTEIN
QUANTITATION
.........................................................................
61
2.2.17
WESTERN
BLOTTING
...............................................................................
61
3
RESULTS
63
3.1
METHODOLOGICAL
REQUIREMENTS
FOR
THE
IDENTIFICATION
OF
CIRCULAR
RNAS
.
.
63
3.2
CIRCRNA
EXPRESSION
CHANGES
THROUGHOUT
HEALTHY
MYELOID
DIFFERENTIATION
65
3.3
SEVERAL
DIFFERENT
CIRCRNA
ISOFORMS
ARE
TRANSCRIBED
FROM
MANY
GENES
IN
HEALTHY
AND
LEUKEMIC
CELLS
......................................................................
70
3.4
RELATIVE
CIRCRNA
ABUNDANCE
IN
HEALTHY
HSPCS
AND
AML
......................
74
3.5
CIRCRNA
EXPRESSION
IS
ALTERED
UPON
LEUKEMIC
TRANSFORMATION
............
76
3.6
INVESTIGATION
OF
THE
INTERNAL
STRUCTURE
OF
TARGET
CIRCRNAS
USING
OXFORD
NANOPORE
SEQUENCING
...................................................................................
86
3.7
ROLLING
CIRCLE
TRANSCRIPTION
IS
FREQUENT
DURING
TRANSCRIPTION
OF
CIRCULAR
RNAS
..............................................................................................................
99
3.8
VALIDATION
OF
CIRCRNAS
IN
PRIMARY
PATIENT
SAMPLES
USING
OXFORD
NANOPORE
SEQUENCING
.............................................................................
101
3.9
CIRC
BCL11B
IS
EXCLUSIVELY
EXPRESSED
IN
AML
......................................104
3.10
PATIENTS
WITH
HIGH
CIRC
BCL11B
EXPRESSION
CO-EXPRESSED
T
CELL
SIGNA
TURE
GENES
..................................................................................................
107
3.11
SHRNA-MEDIATED
C RCBCL11B-1
KNOCKDOWN
......................................... 110
3.12
CIRCBCL1
1
B-1
KNOCKDOWN
DOES
NOT
INFLUENCE
BCL1
1
B
PROTEIN
LEVELS
.
111
3.13
CIRCSCLI/B-1
KNOCKDOWN
DECREASES
PROLIFERATION
OF
OCI-AML5
...
112
3.14
C IRCBCLI
1B-1
KNOCKDOWN
DOES
NOT
INCREASE
APOPTOSIS
OR
DIFFERENTIA
TION
OF
OCI-AML5
CELLS
.................................................................................113
4
DISCUSSION
117
4.1
METHODOLOGICAL
PREREQUISITES
FOR
THE
IDENTIFICATION
OF
CIRCULAR
RNAS
..117
4.2
INVESTIGATION
OF
THE
INTERNAL
STRUCTURE
OF
TARGET
CIRCRNAS
USING
OXFORD
NANOPORE
SEQUENCING
.................................................................................118
4.3
ROLLING
CIRCLE
TRANSCRIPTION
IS
FREQUENT
DURING
TRANSCRIPTION
OF
CIRCRNAS121
4.4
CIRCRNA-EXPRESSING
GENES
AND
NUMBER
OF
THEIR
CIRCRNA
ISOFORMS
.
121
4.5
CIRCRNA
EXPRESSION
IN
AML
COMPARED
TO
HEALTHY
HSPCS
............... 123
4.6
EFFECT
OF
MUTATIONS
IN
SPLICING
FACTORS
ON
CIRCRNA
BIOGENESIS
....
125
4.7
C RCBCL11B
EXPRESSION
IN
AML
...............................................................126
4.8
CO-EXPRESSION
OF
LYMPHOID
GENES
IN
CIRCBC/J
7B_HIGH
AML
............ 128
4.9
DIAGNOSTIC
AND
PROGNOSTIC
POTENTIAL
OF
CIRCRNAS
IN
CANCER
................130
4.10
CIRCRNAS
AS
THERAPEUTIC
TARGETS
IN
CANCER
..............................................130
SUMMARY
132
BIBLIOGRAPHY
136
VII
|
| any_adam_object | 1 |
| author | Lux, Susanne |
| author_GND | (DE-588)1192995805 |
| author_facet | Lux, Susanne |
| author_role | aut |
| author_sort | Lux, Susanne |
| author_variant | s l sl |
| building | Verbundindex |
| bvnumber | BV046270849 |
| ctrlnum | (OCoLC)1129405163 (DE-599)DNB1193596416 |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| genre_facet | Hochschulschrift |
| id | DE-604.BV046270849 |
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| indexdate | 2024-07-10T08:40:09Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-031648665 |
| oclc_num | 1129405163 |
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| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | xix, 172 Blätter Illustrationen, Diagramme 30 cm |
| publishDate | 2019 |
| publishDateSearch | 2019 |
| publishDateSort | 2019 |
| record_format | marc |
| spelling | Lux, Susanne Verfasser (DE-588)1192995805 aut Deregulated circular RNA expression in acute myeloid leukemia (AML) Susanne Julia Andrea Lux née Hirsch Ulm 2019 xix, 172 Blätter Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Ulm University 2018 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1193596416/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031648665&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Lux, Susanne Deregulated circular RNA expression in acute myeloid leukemia (AML) |
| subject_GND | (DE-588)4113937-9 |
| title | Deregulated circular RNA expression in acute myeloid leukemia (AML) |
| title_auth | Deregulated circular RNA expression in acute myeloid leukemia (AML) |
| title_exact_search | Deregulated circular RNA expression in acute myeloid leukemia (AML) |
| title_full | Deregulated circular RNA expression in acute myeloid leukemia (AML) Susanne Julia Andrea Lux née Hirsch |
| title_fullStr | Deregulated circular RNA expression in acute myeloid leukemia (AML) Susanne Julia Andrea Lux née Hirsch |
| title_full_unstemmed | Deregulated circular RNA expression in acute myeloid leukemia (AML) Susanne Julia Andrea Lux née Hirsch |
| title_short | Deregulated circular RNA expression in acute myeloid leukemia (AML) |
| title_sort | deregulated circular rna expression in acute myeloid leukemia aml |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1193596416/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031648665&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT luxsusanne deregulatedcircularrnaexpressioninacutemyeloidleukemiaaml |
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