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Exploring the role of GATA2 in normal and malignant haematopoiesis

Menendez Gonzalez, Juan Bautista 2017. Exploring the role of GATA2 in normal and malignant haematopoiesis. PhD Thesis, Cardiff University.
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Abstract

Haematopoietic stem cells (HSCs) are multipotent stem cells that sustain long-life haematopoiesis. External signals delivered from the bone marrow (BM) niche are crucial for HSC homeostasis, alongside a cell intrinsic transcriptional program driven by transcription factors (TFs). Translocations, epigenetic and genetic mutations altering TF activity, subvert HSC homeostasis leading to the development of preleukaemic stem cells (pre-LSCs) and LSCs that drive the development and maintenance of acute myeloid leukaemia (AML). Gata2, a zinc finger TF expressed in the haematopoietic system, is essential for the generation and survival of HSCs in development, however the requirement for Gata2 in adult HSCs is less clear. Perturbation of GATA2 function by loss of function mutations of the GATA2 gene, gives rise to immunodeficiency syndromes with a high risk of transformation to myelodysplastic syndrome and AML. Conversely, overexpression of GATA2 is observed in approximately 40% of AML patients and has been linked with poor prognosis. However, the precise biological impact of GATA2 expression on AML cell fate, including LSCs, has yet to be interrogated.

Item Type: Thesis (PhD)
Date Type: Submission
Status: Unpublished
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Subjects: Q Science > Q Science (General)
Funders: Life Sciences Research Network Wales, Sêr Cymru Richard Whipp
Date of First Compliant Deposit: 9 March 2018
Last Modified: 04 May 2019 01:57
URI: http://orca.cf.ac.uk/id/eprint/109670

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