Wellcome Trust PhD Programme for Clinicians at the University of Cambridge. (360G-Wellcome-103391_Z_13_A)

Diffuse large B cell lymphoma (DLBCL) is the commonest Non Hodgkin Lymphoma (NHL) among adults and despite aggressive chemoimmunotherapy ~40% of patients die of their disease. The heterogeneity of clinical response is likely representative of biologically distinct subtypes with distinct oncogenic pathways. Phosphoinositide-3 kinases (PI3Ks) are key cellular signalling proteins that act as a central node relaying signals from cell surface receptors to downstream mediators such as AKT. Activation of the PI3K pathway is an important component of normal BCR signalling and has been implicated in the pathogenesis of DLBCL. The first key goal of this research is to further define the role of PI3K pathway in DLBCL by examining signalling, metabolic, apoptotic and stromal interactions to further characterize PI3K as a potentialtarget in treatment of DLBCL. Secondly, we hope to define the metrics of the B cell repertoire in DLBCL using BCR sequencing with the aim of using a BCR clone detected at diagnosis for subsequent response to treatment and minimal residual disease monitoring.