UMR 1170 - Transcriptional and epigenetic control of Malignant Hematopoiesis
The haematopoietic system provides a unique model for investigating how a somatic stem cell can lead to the regulated production of a huge number of differentiated cells and how mutations triggers the development of malignancies. Adult haematopoiesis is organised as cell hierarchy having at its top, a haematopoietic stem cell (HSC) whose functions are tightly regulated by a specific microenvironment mainly located in the bone marrow for the HSC. The current technologies (xenograft, mouse models, next generation sequencing, etc…) enable the thorough analyses of the dynamic of accumulation of the oncogenic hits and their functional consequences during cellular differentiation or transformation.
Classifications of haematological disorders have been initially based on clinical, immunological and cytological data, including differentiation pathway (myeloid versus lymphoid) and stage of differentiation. Some genetic hits are specific for a malignant subtype, whereas some are spread over all types. In addition, haematological disorder subtypes differ between infancy, childhood and adulthood. A growing body of evidence indicates that adult malignancies, both acute and chronic diseases, and both myeloid and lymphoid develop on a pre-leukaemic phase, from of apparently normal progenitors carrying somatic mutations.
We are investigating the genetic aspects of both malignant and non-malignant haematological diseases and analysing their consequences in normal haematopoietic and malignant transformation using up-to-date modelling approaches..
The laboratory is divided into two teams: