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DOI: 10.1055/s-0032-1310468
Lentiviralmarking as a tool to investigate the clonal complexity and evolution of ALL
Introduction: There remains significant controversy over the applicability of cancer stem cell models to acute lymphoblastic leukaemia. Recent data suggest that the propagating compartment undergoes a clonal evolution process, leading to the co-existence of several different subclones.
Methods: We aim to provide a comprehensive picture of the clonal complexity and evolution of ALL by lentivirally marking individual leukaemia cells with heritable genetic markers. This will be achieved using a cellular barcoding strategy and analysis of lentiviral insertion sites. This will allow us to address numerous questions, including assessing the number of clones that contribute to leukaemia following grafting into NSG mice and the Darwinian fitness of matched presentation and relapse samples.
Results: The use of ligation mediated PCR successfully identifies integration sites in lentivirally transduced leukaemia cells. This also facilitates investigations into whether lentiviral marking leads to the development of dominant clones through insertional mutagenesis.
Conclusions: Lentiviral marking of leukaemic stem cells is a powerful tool to investigate the in vivo development of leukaemia.