Understanding the dysregulation of megakaryopoiesis in myelofibrosis.

Ryan Collinson

doi:10.26182/tpqc-sf09

Understanding the dysregulation of megakaryopoiesis in myelofibrosis.

Ryan Collinson

Research output: Thesis › Doctoral Thesis

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Abstract

Myeloproliferative neoplasms (MPN) consist of indolent subtypes polycythemia vera (PV) and essential thrombocythemia (ET) that can progress to myelofibrosis (MF), an aggressive subtype where the marrow becomes scarred. Megakaryocytes are abnormal in MPN and are thought to play a key role in progression. This thesis supports the hypothesis that genetic, transcriptional, and cell interaction impact megakaryocyte development (megakaryopoiesis), in MF. Specifically, the effect of BOD1L1-downregulation on megakaryocyte polyploidisation, dysregulation of TCF3 expression, and deposition of neutrophil granules during emperipolesis. In doing this, we have an improved pathophysiological understanding of megakaryopoiesis and how it may be altered in MPN andparticularly MF.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Guo, Belinda, Supervisor Fuller, Kathy, Supervisor Linden, Matthew, Supervisor Erber, Wendy, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	19 Dec 2024
DOIs	https://doi.org/10.26182/tpqc-sf09
Publication status	Unpublished - 2024

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THESIS - DOCTOR OF PHILOSOPHY - COLLINSON Ryan James - 2024_
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title = "Understanding the dysregulation of megakaryopoiesis in myelofibrosis.",

abstract = "Myeloproliferative neoplasms (MPN) consist of indolent subtypes polycythemia vera (PV) and essential thrombocythemia (ET) that can progress to myelofibrosis (MF), an aggressive subtype where the marrow becomes scarred. Megakaryocytes are abnormal in MPN and are thought to play a key role in progression. This thesis supports the hypothesis that genetic, transcriptional, and cell interaction impact megakaryocyte development (megakaryopoiesis), in MF. Specifically, the effect of BOD1L1-downregulation on megakaryocyte polyploidisation, dysregulation of TCF3 expression, and deposition of neutrophil granules during emperipolesis. In doing this, we have an improved pathophysiological understanding of megakaryopoiesis and how it may be altered in MPN andparticularly MF.",

keywords = "megakaryocyte, myelofibrosis, myeloproliferative neoplasms, BOD1L1, TCF3, emperipolesis, platelets, gene editing",

author = "Ryan Collinson",

year = "2024",

doi = "10.26182/tpqc-sf09",

language = "English",

school = "The University of Western Australia",

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T1 - Understanding the dysregulation of megakaryopoiesis in myelofibrosis.

AU - Collinson, Ryan

PY - 2024

Y1 - 2024

N2 - Myeloproliferative neoplasms (MPN) consist of indolent subtypes polycythemia vera (PV) and essential thrombocythemia (ET) that can progress to myelofibrosis (MF), an aggressive subtype where the marrow becomes scarred. Megakaryocytes are abnormal in MPN and are thought to play a key role in progression. This thesis supports the hypothesis that genetic, transcriptional, and cell interaction impact megakaryocyte development (megakaryopoiesis), in MF. Specifically, the effect of BOD1L1-downregulation on megakaryocyte polyploidisation, dysregulation of TCF3 expression, and deposition of neutrophil granules during emperipolesis. In doing this, we have an improved pathophysiological understanding of megakaryopoiesis and how it may be altered in MPN andparticularly MF.

AB - Myeloproliferative neoplasms (MPN) consist of indolent subtypes polycythemia vera (PV) and essential thrombocythemia (ET) that can progress to myelofibrosis (MF), an aggressive subtype where the marrow becomes scarred. Megakaryocytes are abnormal in MPN and are thought to play a key role in progression. This thesis supports the hypothesis that genetic, transcriptional, and cell interaction impact megakaryocyte development (megakaryopoiesis), in MF. Specifically, the effect of BOD1L1-downregulation on megakaryocyte polyploidisation, dysregulation of TCF3 expression, and deposition of neutrophil granules during emperipolesis. In doing this, we have an improved pathophysiological understanding of megakaryopoiesis and how it may be altered in MPN andparticularly MF.

KW - megakaryocyte

KW - myelofibrosis

KW - myeloproliferative neoplasms

KW - BOD1L1

KW - TCF3

KW - emperipolesis

KW - platelets

KW - gene editing

U2 - 10.26182/tpqc-sf09

DO - 10.26182/tpqc-sf09

M3 - Doctoral Thesis

ER -

Understanding the dysregulation of megakaryopoiesis in myelofibrosis.

Abstract

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