SHORT REPORT Frequency of CBFb/MYH11 fusion transcripts in patients entered into the U.K. MRC AML trials S. E. L ANGABEER , 1 H. WALKER , 1 R. E. G ALE , 1 K. WHEATLEY, 2 A. K. BURNETT, 3 A. H. G OLDSTONE 1 AND D. C. L INCH 1 on behalf of the MRC Adult Leukaemia Working Party 1 Department of Haematology, UCL Hospitals, London, 2 Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, and 3 Department of Haematology, University of Wales College of Medicine, Cardiff Received 18 November 1996; accepted for publication 26 November 1996 Summary. 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 CBFb/MYH11 fusion transcripts by cytogenetic and RT-PCR techniques respect- ively. 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 CBFb/MYH11 fusion transcripts in our study have 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 CBFb/MYH11 fusion transcripts should be mandatory in all cases of AML at diagnosis. Keywords: AML, inv(16)(p13q22), CBFb/MYH11, prognosis. The chromosomal abnormality inv(16)(p13q22) is most closely associated with the distinct subtype of acute myelomonocytic leukaemia with bone marrow eosinophilia (AML M4Eo) (Le Beau et al, 1983) and although the eosinophilia is variable it has been shown to be part of the leukaemic cell population. This pericentric inversion and the t(16;16)(p13;q22) produce a transcriptionally active fusion gene (5 0 -CBFb/MYH11-3 0 ) derived from the CBFb and MYH11 genes at 16q22 and 16p13 respectively. The reciprocal 5 0 -MYH11/CBFb-3 0 product is expressed in a proportion of cases only. The 5 0 -CBFb/MYH11-3 0 chimaeric protein is believed to induce leukaemic transformation by its abnormal interaction with the DNA-binding protein coded by the AML1 gene, thus altering target genes usually regulated by the CBFb/AML1 transcription factor complex (Liu et al, 1995). It has now been established from analysis of data from the MRC AML 10 trial and other international groups that AML patients with the inv(16)(p13q22) translocation, together with those in which the t(15;17)(q22;q21) or t(8;21) (q22;q22) are seen, have a favourable prognosis (Burnett et al, 1995), with the main benefit seeming to be in disease- free survival (DFS) which leads to a better overall survival. This has been incorporated into the ongoing AML 12 trial where good-prognosis patients are spared bone marrow transplantation in first complete remission (CR). It is therefore highly desirable to define those patients who possess these favourable translocations, either by routine cytogenetic investigations or by testing at the molecular level. This may give prognostic information and also provide a means of minimal residual disease evaluation. Conven- tional cytogenetic methods, including synchronization and Giemsa banding, are used to detect specific chromosomal aberrations but visualization of the inv(16)(p13q22) trans- location may be difficult if the metaphase preparations are of a poor quality. It is thus likely that some cases of inv(16)(p13q22) are undetected at diagnosis and patients assigned to the wrong prognostic category. This is particu- larly likely to occur if the morphology is not M4Eo which attracts a high index of suspicion for inv(16)(p13q22). British Journal of Haematology , 1997, 96, 736–739 736  1997 Blackwell Science Ltd Correspondence: Professor D. C. Linch, Department of Haematology, University College London Medical School, 98 Chenies Mews, London WC1E 6HX.