David Grimwade

I am interested in the molecular mechanisms underlying the pathogenesis of acute promyelocytic leukaemia (APL), which is one of the commonest forms of acute myeloid leukaemia (AML). APL is characterised by the t(15;17)(q22;q21) chromosomal translocation which fuses the genes encoding PML and Retinoic Acid Receptor Alpha (RARA). APL is of particular interest, being the first form of leukaemia in which therapies (ie all trans retinoic acid (ATRA) and arsenic trioxide) that specifically target the underlying molecular lesion, and which have led to dramatic improvements in outcome of this disease, were introduced into clinical practice.

My research focuses particularly upon characterizing the mechanisms underlying formation of the t(15;17) chromosomal translocation which represents a critical step in leukaemogenesis, defining the progenitors in which this occurs, and the role of deregulation of the PML protein in leukaemic transformation. The laboratory also acts as the National Reference Centre for Molecular Diagnosis of APL, providing a minimal residual disease (MRD) monitoring service to direct patient treatment.