Cancer Institute Seminar Series - Prof Inderjeet Dokal

Hosted by: Professor Adele Fielding

A diverse range of haematological disorders are unified by haematopoietic failure leading to a life threatening deficiency of mature blood cells. This includes the pathological entities aplastic anaemia (AA), myelodysplasia (MDS) and acute myeloid leukaemia (AML). It is also notable that patients with AA can evolve to MDS and AML. These pathological connections are particularly prominent in patients with inherited predisposition to these haematological diseases. My group has had a long standing interest in the genetics and biology of inherited/genetic haematopoietic disorders such as dyskeratosis congenita. Our studies over the last 25 years have characterized several disease genes, germline defects in which, give rise to haematological phenotypes ranging from bone marrow failure to leukaemia, as well as non-haematological cancers. These genes are important in telomere maintenance (e.g. DKC1 and TERC encoding telomerase), ribosome biogenesis (e.g. DNAJC21) and DNA repair (e.g. ERCC6L2).

These findings demonstrate how key biological pathways are important in normal haematopoiesis and whose disruption is the primary driver of the complex haematological disease. Secondly, they have demonstrated that some cases of AA, MDS or AML are in fact arising from a germline genetic defect in one or other of these disease genes. For example, germline telomerase mutations account for a subset of idiopathic AA, MDS and AML. These observations have implications for the diagnosis and management (e.g. in the selection of appropriate family stem cell donors and design of conditioning regimens) of new patients presenting in the clinic with de novo AA, MDS and AML. They also highlight the important inherited/genetic contribution in AA, MDS and AML, paving the way to new therapeutic strategies.

• Professor Inderjeet Dokal academic profile

A light lunch will be served after the seminar. This seminar has been sponsored in part by the Biomedical Research Centre and Cancer Research UK

Main image - SEM of red blood corpuscles, close-up. Credit: David Gregory & Debbie Marshall.