Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

Periodic Report Summary 1 - ONCINDLYMPH (Oncogene-induced DNA damage as driver of B cell lymphoma genesis)

Leukaemia arises from healthy cells of the immune system. The progression from a healthy cell to the terminally cancerous cell coincides with acquisition of defined defects in the DNA of the leukaemia cell or precursor cell that promote the disease, a process termed clonal evolution of cancer. The reason for the occurrence of these secondary disease-promoting defects in leukaemia is still in debate. Activation of cancer genes is prominent in pre-malignant and malignant cells, and cancer gene-induced cellular stress, a process known to damage DNA, is assumed to represent a likely cause of disease-promoting genomic lesions. However, direct evidence to support this model in leukaemia cells is still missing. The laboratory of Dr Feldhahn functionally characterizes the relevance of cancer stress for leukaemia initiation and progression. Further, the group of Dr Feldhahn analyses the progression of leukaemia precursor cells towards successful transformation for occurrence of so far unknown genomic events that promote tolerance to cancer stress.
Since the start of this Marie Curie CIG funded project, we analysed cancer gene induced leukaemia precursor cells in a genome-wide approach for ongoing genomic instability. We could identify >1000 regions in the genome of leukaemia initiating cells that are sensitive to DNA damage resulting from cancer stress, including a high number of those frequently defective in leukaemia patients. Using functional next-generation-sequencing-based approaches we could characterise a so far unknown mechanism of cancer gene-induced genomic instability that may explain why some genes are especially prone to become defective in some leukaemia subtypes but not in others. A detailed manuscript on these findings is under preparation.
With the help of the Marie-Curie Career Integration Grant (CIG) the laboratory of Dr Feldhahn is now fully established at the Department of Medicine at Imperial College London (ICL). Funding by UK-based charities together with European Commission-based funding allowed Dr Niklas Feldhahn to become a Principal Investigator (PI) with the prospect of tenure position at ICL.

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United Kingdom
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