Holdings: The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms

The role of the histone demethylases LSD1 and JMJD1C in the pathophysiology of myeloproliferative neoplasms:

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Bibliographic Details
Main Author:	Jutzi, Jonas Samuel 1986- (Author)
Format:	Thesis Book
Language:	English
Published:	Freiburg im Breisgau May 2018
Subjects:	Hochschulschrift
Online Access:	Inhaltsverzeichnis Inhaltsverzeichnis
Item Description:	Enthält Zeitschriftenaufsätze
Physical Description:	III, 108 Seiten Illustrationen, Diagramme 30 cm

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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
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author	Jutzi, Jonas Samuel 1986-
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format	Thesis Book
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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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