Molecular abnormalities in B-cell chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia is the commonest adult leukaemia, however the pathogenesis is largely unknown. Since the 1980s specific chromosomal abno rmalities have been identified, of which the commonest are deletions of chr omosomes 6q, 11q23, 13q14 and 17q13 and trisomy 12, The search for the resp onsible oncogenes at these sites has proved to be extremely frustrating, Th ere are many oncogenes at 11q23 but the exact gene(s) responsible have yet to be identified. Germline abnormalities of the ATM gene occur in about 18% of patients compared to a normal population carriage of 0.5% but not all s tudies agree that ATM is the gene responsible. Unfortunately, despite the identification of various minimally deleted regi ons and the full sequencing of 13q14 no oncogenes have been identified. All original studies suggested the presence of a autosomally recessive tumour suppressor gene at this site but more recent studies suggest this may not b e the case and the pathogenesis is more complex than first thought. Similarly, no genes have been identified at 6q or on chromosome 12. We know that the p53 tumour suppressor gene at 17p13 is an important prognostic in dicator but it occurs in a minority of patients (about 15%), usually in pat ients with advanced disease, and therefore probably is not of aetiological importance.