Detection of inv(16) and t(16;16) by fluorescence in situ hybridization inacute myeloid leukemia M4Eo

Background and Objectives. It has been established that cytogenetic finding s at the time of diagnosis of acute myeloid leukemia (AML) are powerful pro gnostic indicators. Pericentric inversion of chromosome 16 and translocatio n t(16;16) resulting in chimeric fusion of CBFB and MYH11 genes are typical ly seen in the M4-Eo FAB classification subset of AML and are associated wi th low-risk disease. These subtle chromosomal abnormalities may be difficul t to detect in poor-quality metaphase preparations and if missed could lead to incorrect assignment to risk groups and influence the therapy decision- making process. Design and Methods. We prospectively studied, at diagnosis, 10 patients wit h AML-M4 Eo by cytogenetics and fluorescent in situ hybridization (FISH) wi th two cosmids (36 and 40), As a control group, 7 patients (5 with a diagno sis of AML other than M4 Eo and two cases of reactive eosinophilia) were an alyzed. In addition reverse transcriptase chain reaction (RT-PCR) studies w ere carried out in 6 cases. Results. Karyotypic analysis detected the inv(16) in all but one of the pat ients with M4-Eo while none of the control cases showed any abnormality on chromosome 16, FISH studies showed that all 10 patients had abnormalities o n chromosome 16; the patient with normal karyotype showed an inv(16) by FIS H, while a case with inv(16) by cytogenetics had a t(16;16) by FISH. RT-PCR demonstrated amplification of the CBFB/MYH11 product in all cases analyzed , Interpretation and Conclusions. In patients with M4Eo and rearrangements of chromosome 16, FISH studies may afford more complete information than conv entional cytogenetics and can be an alternative to RT-PCR studies. (C) 2000, Ferrata Storti Foundation.