The role of NFIA fusion genes in erythroid leukaemia

It is clear that the process of haematopoietic (blood) development is ultimately coordinated by transcription factors, a view supported by the prevalence of transcription factor abnormalities found in leukaemia. Although gradual improvements in combination chemotherapy regimens and supportive care strategies have achieved a significant increase in survival rates in many acute leukaemias, the majority of patients continue to die from their disease and are a significant healthcare challenge. Acute erythroleukemia (AEL) is a rare but aggressive human blood cancer characterized by uncontrolled accumulation of erythroid progenitor cells. Cytogenetic analysis of leukaemic cells from pediatric patients with AEL revealed a chromosomal translocation t(1;16)(p13;q24) leading to the expression of NFIA::ETO2. More recently (2023), a novel t(1;8)(p13;q21) translocation fusing NFIA to RUNX1T1 has also been identified in pediatric AEL, suggesting the importance of these translocated products in the pathogenesis of this disease.

The overall goal of this study is to gain a detailed understanding of the effect of NFIA::RUNX1T1 or NFIA::ETO2 on the development of primitive human primary blood cells. To achieve this, the student will utilize our previously devised experimental model based on normal human blood progenitor/stem cells. Here, the student will analyse the effects of these translocations (independently) on blood cell growth, development, differentiation, cell survival and self-renewal. Further, a mechanistic understanding of how haematopoietic development is disrupted by these translocations will lead to new approaches for therapeutic intervention and may identify prognostic indicators AEL.

 The student will be based in Cardiff’s Blood Cancer Research UK Centre of Excellence within the Section of Haematology, DCG. The main research interest of the Department is haematological oncology, which has consistently submitted an outstanding International Profile for the REF assessments. The proposed supervisory team have a strong track record of research collaboration centred on understanding how molecular abnormalities associated with leukaemia contribute to disease pathogenesis. The proposed supervisors have been trained in supervision and have an excellent record of completion as well as progression of students to academic research.

 Training environment

The candidate will also be part of the Division of Cancer and Genetics (DCG) in the School of Medicine, based at the Heath Park Campus, Cardiff. It has around 150 staff and 40 PGR students, housed in four research buildings with well-equipped laboratories. Researchers within the Division also have access to Bioinformatic support through the Wales Gene Park, and the potential to collaborate with colleagues in the NHS All Wales Medical Genetics Service. As well as being a major contributor to School events, the Division has it’s own weekly seminar program where students, post-docs, clinical research fellows and lab heads present their research. There is also an annual DCG PGR research day, which features student talks and a social event led by students. All PhD students in the School of Medicine undergo a week training course with additional modules over several months in research methods and will have access to several courses on research skills through the Doctoral Academy. The School of Medicine currently has a 95% completion rate for PhD submissions.

For more project details email TonksA@cardiff.ac.uk

Entry Requirements  

Applicants should possess a minimum of an upper second class Honours degree, master’s degree, or equivalent in a relevant subject. 

Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS). 

How to Apply  

This studentship has a start date of October 2024. In order to be considered you must submit a formal application via Cardiff University’s online application service.

There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2024). This will take you to the application portal. 

In order to be considered candidates must submit the following information: 

 • Supporting statement 

• CV 

• Qualification certificates 

• References x 2 

• Proof of English language (if applicable) 

International applicants are welcomed if the difference in fees can be covered.