Effects of bone marrow stromal cells on sensitivity of leukaemic cells to chemotherapy

Page, K; Anderson, E; Smith, A; Reid, C; Salisbury, V; Donaldson, C; May, J E

Abstract

Cytosine arabinoside (ara-C) is a key chemotherapy drug used to treat acute myeloid leukaemia (AML), however, ap- proximately 30% of patients do not respond to this therapy.
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An evaluative assay to determine resistance/sensitivity to ara- C prior to chemotherapy treatment would reduce unnecessary exposure to the cytotoxic and other side effects of ineffective treatment for patients shown to be resistant. Collaboration between the University of the West of England and Randox Laboratories Ltd has developed a bacterial bioluminescence- based biosensor for rapid evaluation of patient leukaemic cell susceptibility to ara-C. However, in up to 10% of patient sam- ples there is low correlation between biosensor results and patient outcome. In in-vitro assays, both conditioned media from, and co-cultures with, bone marrow stroma have pre- viously been found to affect the sensitivity of AML cells to chemotherapy and may be a factor affecting this correlation. To evaluate whether the presence of bone marrow stromal cells affect the sensitivity of AML cells using the biosensor assay, co-cultures of stromal and leukaemic cell lines were conducted using cell culture inserts and compared to each cell type alone. Genotoxicity and cytotoxicity of stromal (HS-5) and AML cell lines (HL60, HEL and K562) were measured by the comet as- say and viability stains, respectively, and compared with the sensitivity of the cell types to ara-C using the biosensor assay. Pilot data indicate that ara-C induced a loss of both viability and proliferation in stromal cells and in AML cell lines known to be sensitive to ara-C. Stromal-AML co-cultures did not re- duce this loss of viability in either cell type. However, the bio- sensor assay indicated decreased sensitivity of AML cells to ara-C when in co-culture compared to AML cells alone. This study may increase the accuracy of the bioluminescence bio- sensor for rapid evaluation of patient sensitivity to ara-C, prior to chemotherapeutic treatment.

• Journal Article Type: Article
• Acceptance Date: Jul 15, 2013
• Online Publication Date: Dec 18, 2013
• Publication Date: Jan 31, 2014
• Deposit Date: Apr 25, 2017
• Journal: Mutagenesis
• Print ISSN: 0267-8357
• Electronic ISSN: 1464-3804
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 1
• Pages: 92
• DOI: https://doi.org/10.1093/mutage/get060
• Keywords: bone marrow stromal cells, sensitivity, leukaemic cells, chemotherapy
• Public URL: https://uwe-repository.worktribe.com/output/821774
• Publisher URL: http://dx.doi.org/10.1093/mutage/get060
• Contract Date: Apr 25, 2017