MOLECULAR-DETECTION OF T(8-21) AML1-ETO IN AML M1/M2 - CORRELATION WITH CYTOGENETICS, MORPHOLOGY AND IMMUNOPHENOTYPE/

The t(8;21) identifies a subgroup of acute myeloid leukaemia (AML) wit h a relatively good prognosis which may merit different treatment, It is associated predominantly, but not exclusively, with AML M2, and cor responds to rearrangements involving the AML1 and ETO genes. AML1-ETO positive, t(8;21) negative cases are well recognized but their inciden ce is unknown, In order to determine optimal prospective AML1-ETO RT-P CR screening strategies, we analysed 64 unselected AML M1 and M2 cases and correlated the results with other biological parameters, Molecula r screening increased the overall detection rate from 8% to 14%, AML1- ETO was found in 3% (1/32) of AML M1 and 25% (8/32) of M2, including t hree patients without a classic t(8;21) but with chromosome 8 abnormal ities. It was more common in younger patients. Correlation with morpho logy enabled development of a scoring system which detected all nine A ML1-ETO-positive cases with a false positive rate of 7% (4/55), Althou gh certain AML1-ETO-positive cases demonstrated characteristic immunol ogical features (CD19 and CD34 expression CD33 negativity), each of th ese markers was insufficiently specific to permit prediction in an ind ividual case. We conclude that initial routine prospective molecular s creening for AML1-ETO in all AMLs, combined with standardized morpholo gical and immunological analysis, is desirable in order to produce imp roved prognostic stratification and to determine whether screening can ultimately be restricted to appropriate subgroups.