Use of immunohistochemistry and co-culture model systems to investigate the contribution of M2 macrophages towards chemotherapy resistance in patients with Acute Myeloid Leukaemia

  • Williams, Mark (PI)
  • Copland, Mhairi (CoI)
  • Orange, Claire (CoI)
  • Konopleva, Marina (CoI)

Project Details

Description

Resistance to cancer drugs (chemoresistance) is one of the main reasons for poor survival in Acute Myeloid Leukaemia (AML); one of the most common blood cancers in adults. Cross-talk between blood cancer cells, and other cells present within the bone marrow (NM), significantly contributes towards chemoresistance. Cancer-supporting macrophages (type of immune cell) are present in high numbers in the BM of blood cancer patients (e.g. Multiple Myeloma), and have been shown to contribute towards chemoresistance. Our initial findings from our collaborative studies suggest that cancer-supporting macrophages are increased in the BM of AML patients compared to healthy individuals. Additionally, both direct culture of leukaemic cells together with macrophages, as well as substances produced from macrophages, can protect AML cells from cancer drugs. Firstly, using staining methods and advanced analysis software to assess macrophage numbers in additional BM samples from AML patients and healthy individuals, we will confirm and consolidate our initial pilot findings. Secondly, utilising co-culture systems comprised of primary AML samples (cells obtained directly from patients), and macrophages, we will determine if macrophages contribute to chemotherapy resistance in AML, and uncover new targetable chemoresistance mechanisms. Importantly, these studies will therefore drive the development of much needed new drugs to effectively treat, and improve the survival of AML patients.
Short titleimmunohistochemistry and co-culture model systems
StatusFinished
Effective start/end date1/11/1831/05/20

Funding

  • Tenovus Scotland: £12,000.00

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