Acute Myeloid Leukaemia
Bone marrow is a complex three-dimensional (3D) tissue wherein haematopoiesis is regulated by spatially organised cellular microenvironments (niches). Dysregulation of these niches, either in structure or function, is implicated in the pathogenesis of disease states of the bone marrow, such as Acute Myeloid Leukaemia (AML), an aggressive bone marrow cancer. Although 2D in vitro cultures and in vivo animal models of AML and clonal haematopoietic neoplasms have helped to elucidate the molecular determinants of disease, the cellular and microenvironmental elements integral to this process are difficult to decipher based on the limitations of these same techniques.
Dr Panoskaltsis and colleagues have developed novel 3D bone marrow culture systems in static and continuous perfusion bioreactors that simulate the in vivo 3D growth environment and support multi-lineage haematopoiesis in the absence of exogenous growth factors or serum, making them useful tools for the study of normal haematopoiesis and bone marrow disease states. They are now using these ex vivo platforms for the development of human experimental models for the study of normal haematopoiesis, primary leukaemia biology and leukaemia immune pathogenesis in vitro and to inform personalised chemotherapy protocols in a patient-specific, leukaemia-specific manner with the aid of mathematical modelling tools (in silico) which have also been developed by this group.
The work takes place in the Biological Systems Engineering Laboratory (http://www.imperial.ac.uk/bsel) located in the Department of Chemical Engineering. The largest research component within the group is the Blood Programme, a dynamic interdisciplinary research group comprised of investigators from the fields of Haematology, Medical & Biological Sciences, Chemical Engineering and Computational Mathematics all working together in an exciting and interactive environment. The ultimate goal of the research programme is to rapidly translate the in vitro-in silico discoveries and personalised therapies developed by the group using standard and novel immunochemotherapeutics into in vivo protocols for optimised, more effective and less toxic treatments for patients with AML.