Investigating the contribution of macrophages

towards chemotherapy resistance in Acute Myeloid Leukaemia

Project reference number: HLSLTC008

Background

Acute Myeloid Leukaemia (AML) is one of the most common adult blood cancers. Survival rates for the majority of adult AML patients are poor (<20%): remaining largely unchanged over the last 40 years (https://www.hmrn.org/statistics/survival) long-term Chemotherapy resistance (chemoresistance) significantly contributes towards poor survival in AML, and is strongly influenced by cells within the bone marrow (BM). Our initial findings suggest that cancer-supporting macrophages are increased in the BM of AML patients. Additionally, culture of AML cells together with these macrophages protects AML cells from cell death, normally induced by standard AML chemotherapy.

Studies investigating chemoresistant mechanisms in AML have mainly employed traditional co-culture methods that fail to reproduce chemoresistant features of the BM (e.g. low oxygen levels). To gain a better understanding of the underlying biology, and assess the effectiveness of novel therapeutic agents, it is essential to use novel co-culture systems. These systems more accurately reflect the conditions and architecture within the BM.

Example references

Burnett, A. K. Hematology Am Soc Hematol Educ Program 2012, 1–6 (2012).

Gao, L., Yu, S., and Zhang, X. (2014). Cell Biochem Biophys 70, 273–277.

Aim

This study will determine the mechanisms underlying macrophage-mediated chemoresistance in AML.

  • We will utilise a unique model system and clinically applicable agents, provided by our academic (Cornell University), and biopharmaceutical (AstraZeneca) links.
  • This study will discover novel drug targets, leading to the development of safer and more effective treatment strategies crucially required for AML, and potentially other blood cancers.
  • Ultimately this research will lead to improved clinical outcomes, including quality of life and long-term survival in blood cancer patients.

Application deadline

The application deadline for October intake is 1st of July.

Research supervisors

Candidates are encouraged to contact the following researchers for further details:

Modes of study

This project is available as a:

  • PhD: 3 years full-time.
  • 1 + 3 route to PhD: Undertaking MRes [1 year full-time] + PhD as above

Eligibility

Applicants will normally hold a UK honours degree 2:1 (or equivalent); or a Masters degree in a subject relevant to the research project. Equivalent professional qualifications and any appropriate research experience may be considered. A minimum English language level of IELTS score of 6.5 (or equivalent) with no element below 6.0 is required. Some research disciplines may require higher levels.

Specific requirements of the project

The successful applicant will have a strong interest in exploring therapeutic strategies for the treatment of Leukaemia/Acute Myeloid Leukaemia, and hold a minimum of a first degree (2:1) or above, ideally in Cell Biology, Biochemistry or Molecular Biology or combinations thereof. Experience in molecular biology (e.g. immunoblotting, qPCR and flow cytometry) or cell culture techniques (e.g. culturing adherent and/ suspension cell lines/ primary cells), would be an advantage.