The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms:
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Freiburg im Breisgau
May 2018
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| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | Enthält Zeitschriftenaufsätze |
| Beschreibung: | III, 108 Seiten Illustrationen, Diagramme 30 cm |
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| 100 | 1 | |a Jutzi, Jonas Samuel |d 1986- |e Verfasser |0 (DE-588)1047152088 |4 aut | |
| 245 | 1 | 0 | |a The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms |c presented by Jonas Samuel Jutzi |
| 264 | 1 | |a Freiburg im Breisgau |c May 2018 | |
| 300 | |a III, 108 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
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| 500 | |a Enthält Zeitschriftenaufsätze | ||
| 502 | |b Dissertation |c Albert-Ludwigs-Universität Freiburg im Breisgau |d 2018 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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Datensatz im Suchindex
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| adam_text | I
TABLE OF CONTENTS
LIST OF FIGURES
........
.
...........................................................................................................
ILL
LIST OF TABLES..........................................................
ILL
1
INTRODUCTION................................................................................................................
1
1.1 E
PIGENETICS
..............................................................................................1
1.1.1 DNA METHYLATION
...................................................................................................
1
1.1.2 HISTONE MODIFICATION
.............................................................................................
3
1.1.2.1 HISTONE
ACETYLATION..................................................... 4
1.1.2.2 HISTONE
PHOSPHORYLATION.......................................................................................................5
1.1.2.3 HISTONE
METHYLATION..............................................................................................................5
1.1.2.4 HISTONE
DEMETHYLATION..........................................................................................................6
1.1.3 THE HISTONE DEMETHYLASE LSD1
............................................................................
7
1.1.3.1 LSDTS INFLUENCE ON NON-HISTONE
PROTEINS.....................................................
.
....................7
1.1.3.2 LSD1 AS DRUGGABLE TARGET IN MYELOID
MALIGNANCIES...........................................................8
1.1.4 THE HISTONE DEMETHYLASE JMJD1C
........................................................................9
1.1.4.1 JMJD1C AS DRUGGABLE TARGET IN MYELOID
MALIGNANCIES.....................................................10
1.2 H
EMATOPOIESIS
.......................................................................................
10
1.2.1 HEMATOPOIESIS FROM AN EPIGENETIC POINT O F VIEW.
....................................
12
1.2.2 THE TRANSCRIPTION FACTOR NFE2
...........................................................................
14
1.3 M
YELOPROLIFERATIVE
N
EOPLASMS
.........................................................14
1.3.1 MOLECULAR PATHOGENESIS OF MYELOPROLIFERATIVE NEOPLASMS
.............................
16
1.3.1.1 THE ROLE OF JAK2 AND JAKZ
VSUF
IN
MPN............................................................................
16
1.3.1.2 THE MUTATIONAL LANDSCAPE OF MPN, INCLUDING MPL AND
CALR........................................17
1.3.2 POLYCYTHEMIA VERA
..............................................................................................
18
1.3.3 ESSENTIAL THROMBOCYTHEMIA
..............................................................................
20
1.3.4 PREFIBROTIC MYELOFIBROSIS AND OVERT MYELOFIBROSIS
..............................
21
1.3.5 CURRENT TREATMENT OPTIONS FO R ET, PV AND PMF.
.............................................
24
1.3.5.1 TREATMENT OF
PV...................................................................................................................25
1.3.5.2 TREATMENT OF
ET...................................................................................................................
26
1.3.5.3 TREATMENT OF
PMF................................................................................................................
27
1.3.6 THE TRANSCRIPTION FACTOR NFE2 IN THE CONTEXTOFMPNANDAML
................
...28
2
LSD1 INHIBITION PROLONGS SURVIVAL IN MOUSE MODELS OF MPN BY
SELECTIVELY TARGETING THE DISEASE CLONE
......................................
.
.................
29
2.1 A
IM
AND
SIGNIFICANCE
OF
THE
STUDY
.....................................................
29
2.2 M
ANUSCRIPT
(P
APER
P
ROOF
)
..............................................................
30
3 EPIGENETIC REGULATION OF NFE2 OVEREXPRESSION IN
MYELOPROLIFERATIVE
NEOPLASMS.............................................................................45
3.1 A
IM
AND
SIGNIFICANCE
OF
THE
S T U D Y
...................................................
45
3.2 M
ANUSCRIPT
............................................................................................46
4
DISCUSSION.......................................................................................................................63
4.1
LSD1
AND BENIGN HEMATOPOIESIS
............................................
V
.....................
63
4.1.1 KNOWN MECHANISMS.
.......................
63
4.1.1.1 GFI1B AND
LSD1....................................................................................................................
63
4.1.1.2 LSD1 IN THE CONTEXT OF CELL-CYCLE REGULATION AND APOPTOSIS
............................................
65
4.1.2 POTENTIAL NEW MECHANISMS
.................................................................................67
4.1.2.1 LSD1 AND PLATELET
FORMATION................................................................................................67
4.1.2.2 LSD1 AND
FIBROSIS..................................................................................................................69
4.1.3 LSD1 AND INFLAMMATION
......................................................................................
69
4.2
LSD1
IN MALIGNANT HEMATOPOIESIS AND SOLID TUMORS
.........................
70
4.2.1 LSD1 INHIBITION AND DIFFERENTIATION
-
NOVEL MECHANISM FROM AM L
.............
70
4.2.2 LSD1 AND HIFI
-
KNOWN MECHANISM FROM SOLID TUMORS
................................
72
4.2.3 POTENTIAL NEW TREATMENT STRATEGIES
..................................................................
72
4.3
JMJD1C
IN THE CONTEXT OF
MPN
......................................................................
73
4.4
JMJD1C
AND
LSD1
ARE IMPORTANT FACTORS IN THE
DNA
DOUBLE-
STRANDED BREAK REPAIR MACHINERY
............................................................................
74
4.4.1 JMJD1C REGULATES THE RAP80-BRCA1 BRANCH O F DDR AT THE MDC1 LEVEL.
....
75
4.4.2 LSD1 REGULATES THE RAP80-BRCA1 BRANCH O F DDR DOWNSTREAM
OFRNF16876
4.4.2.1 IMPAIRED DNA DAMAGE RESPONSE AND
JAK2V617F
MUTANT ALLELE BURDEN
..........................
76
4A 2.2 IMPAIRED DNA DAMAGE RESPONSE AND POSSIBLE LEUKEMOGENECITY
..................................
77
4.5
NFE2
IN THE CONTEXT OF MYELOID MALIGNANCIES
.......................................
77
4.5.1 PUTATIVE COOPERATION BETWEEN ENHANCED NFE2 ACTIVITY AND MYC
.................
78
5
CONCLUSIONS...................................................................................................................80
6
SUMMARY.........................................................................................................................
81
7
ZUSAMMENFASSUNG......................................................................................................82
8
ACKNOWLEDGEMENTS.................................................................................................83
9 CURRICULUM VITAE
.
...................
85
10 BIBLIOGRAPHY. 87
|
| any_adam_object | 1 |
| author | Jutzi, Jonas Samuel 1986- |
| author_GND | (DE-588)1047152088 |
| author_facet | Jutzi, Jonas Samuel 1986- |
| author_role | aut |
| author_sort | Jutzi, Jonas Samuel 1986- |
| author_variant | j s j js jsj |
| building | Verbundindex |
| bvnumber | BV045355471 |
| ctrlnum | (OCoLC)1090098999 (DE-599)BSZ508470641 |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| indexdate | 2024-07-10T08:15:50Z |
| institution | BVB |
| language | English |
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| physical | III, 108 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2018 |
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| spelling | Jutzi, Jonas Samuel 1986- Verfasser (DE-588)1047152088 aut The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms presented by Jonas Samuel Jutzi Freiburg im Breisgau May 2018 III, 108 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Enthält Zeitschriftenaufsätze Dissertation Albert-Ludwigs-Universität Freiburg im Breisgau 2018 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1170691358/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030742068&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Jutzi, Jonas Samuel 1986- The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms |
| subject_GND | (DE-588)4113937-9 |
| title | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms |
| title_auth | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms |
| title_exact_search | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms |
| title_full | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms presented by Jonas Samuel Jutzi |
| title_fullStr | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms presented by Jonas Samuel Jutzi |
| title_full_unstemmed | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms presented by Jonas Samuel Jutzi |
| title_short | The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms |
| title_sort | the role of the histone demethylases lsd1 and jmjd1c in the pathophysiology of myeloproliferative neoplasms |
| topic_facet | Hochschulschrift |
| url | http://d-nb.info/1170691358/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030742068&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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