Characterising the genetic changes that arise from DNA damage in leukaemia and lymphoma

Updated 26 Jul 2018
Lead researcher - Dr Niklas Feldhahn, Imperial College London
Cancer type - Leukaemia
Oncogene-induced stress as driver of B cell lymphomagenesis
Amount awarded: £650,000
Award start date: 01 Jun 2013
Award duration: 5 years (60 months)

Cancer cells arise from healthy cells as a result of an unfortunate event that causes malignancy. Specific changes in the DNA that lead to uncontrolled activity of a cancer gene (oncogene) represent such unfortunate events. However, accidental activation of cancer genes occurs regularly in healthy cells without inducing malignancy. Healthy cells sense the presence of cancer genes as they lead to significant changes in the normal metabolism of the cell (cancer stress). As a response, healthy cells undergo suicide or terminally arrest cell division, a mechanism considered as an immediate barrier to prevent malignancy. Unfortunately, some cells pass this barrier leading to overt leukaemia and lymphoma. It is assumed that they do so by the acquisition of further changes in the DNA, which allow the cell to ignore cancer stress. Cancer stress by itself has been shown in many cases to cause damage in the DNA and is highly likely to be the molecular reason for the acquisition of secondary changes that mediate tolerance to cancer genes. The study is designed to identify the changes in the DNA that confer cancer gene tolerance and to develop strategies to reverse these changes in cancer cells. Reactivation of intolerance to cancer genes should lead to lethality in tumour cells and represents a new and promising strategy for the future treatment of leukaemia and lymphoma.