Frequency of CBF beta/MYH11 fusion transcripts in patients entered into the UK MRC AML trials

It has been established that cytogenetic findings at diagnosis of acute myeloid leukaemia (AML) are a powerful prognostic indicator. Patients who have the inv(16)(p13q22), closely associated with the FAB subtype M4Eo, are deemed to have good-risk disease. This subtle translocation may be difficult to detect in poor-quality metaphase preparations and if missed could lead to the incorrect assignment of risk group and influence further treatment strategies. We studied 321 patients with AML at diagnosis for the presence of inv(16)(p13q22) and CBF beta/MYH11 fusion transcripts by cytogenetic and RT-PCR techniques respectively. Karyotypic analysis detected 21 cases of inv(16) (p13q22), all of which were PCR positive. A further 12 cases were detected at the molecular level only, in FAB types other than M4Eo. The observed frequencies of CBF beta/MYH11 fusion transcripts in our study hare been adjusted for the reported incidence of each FAB subtype and we calculate that 10.1% of all new cases of AMLs have molecular evidence of inv(16)(p13q22), only half of which are of the M4Eo subtype. We conclude that molecular screening for the presence of CBF beta/MYK11 fusion transcripts should be mandatory in all cases of AMI, at diagnosis.