The regulation of gene expression is an essential factor in early embryonic development. It is also an integral part of cancer transformation. Not surprisingly, many developmental master genes are closely linked to cancer. In leukemia, for example, the most important regulators of the initial differentiation of hematopoietic stem cells were discovered through their involvement in leukemia-associated chromosomal translocations. This year's lecture revisits these dangerous links.
A few reminders of the genetic origins of cancer were presented, in particular the notion of driver mutation, directly implicated in the development of these pathologies. In the case of leukemia, the number of such drivers can sometimes be very limited - one or two. While the catalog of mutations associated with different forms of cancer is beginning to be well known, the exact cellular functions of these mutants in the cell of origin often remain poorly understood. Proteins altered in cancer are often located at signaling nodes, and therefore control multiple pathways (proliferation, metabolism, apoptosis, senescence, differentiation, migration...). In this context, the exact role of each loss or gain of function associated with a given mutation often remains unclear. The challenge of post-genomics is to explore these different functional facets, which are essential but often neglected steps in the development of targeted therapies.