A study of the poor prognostic genomic alterations affecting 11q and 17p in CLL using CGH arrays
Claire Dearden, M.D.
Royal Marsden Hospital/Institute for Cancer Research
Abstract:
Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia affecting adults in North America and Europe. It is well known that CLL patients who have certain abnormalities in the genes of their leukemic cells respond less well than others to treatment and survive less long. Frozen cells have been stored in the Royal Marsden Cell Bank from the blood or bone marrow of over 700 patients enrolled in the recently closed UK CLL4 trial, which randomly assigned previously untreated CLL patients to treatment with either chlorambucil or fludarabine (with or without cyclophosphamide). The genes in these cells have already been analysed and abnormalities of the “11q” and “17p” gene regions have been found to be linked with poorer outcomes. Only 58% of the 79 patients with deleted 11q genes (and 18% of the 44 with deleted 17p genes) survive for four years, compared to 72% of patients without these abnormalities. In addition, 79% of those with 17p deletions failed to respond to treatment, compared to only 12% of those with “normal” genes. But the course of the disease will not be the same for all patients within these groups.
We propose to use a variety of new, highly sensitive laboratory techniques to:
Map the deletions at 11q and 17p more precisely
Define exactly which genes within these regions are associated with poor outcome
Identify new altered regions, and define which particular malfunctioning genes within them affect outcome
Look for gene abnormalities which affect how CLL cells arise, behave and proliferate, and which may be targets for new treatments.