IDENTICAL FUSION TRANSCRIPT ASSOCIATED WITH DIFFERENT BREAKPOINTS IN THE AML1 GENE IN SIMPLE AND VARIANT T(8-21) ACUTE MYELOID-LEUKEMIA

Fluorescence in situ hybridization (FISH) and/or RNA-based polymerase chain reaction (RT-PCR) were used to analyze the breakpoints within th e AML1 gene and the AML1 fusion transcripts in t(8;21) acute myeloid l eukemia (AML). Twenty-two patients presented with the simple t(8;21)(q 22;q22) and one with a complex variant t(8;2;16;21). In eight cases we used FISH with AML1 cosmid probes on metaphase chromosomes as well as RT-PCR to detect the junctions of AML1/CDR (ETO,MTG8). Five cases wer e analyzed by FISH alone and ten cases by RT-PCR alone. By FISH we cou ld identify three groups according to the distribution of the fluoresc ent signal. Signals were found in group 1 on chromosomes 21 and 21q+, in group 2 on chromosomes 21, 21q+ and 8q- and in group 3 on chromosom es 21 and 8q-. In all groups we could detect an identical AML1/CDR fus ion transcript. This transcript showed splicing of AML1 exon 5 onto CD R. Thus regardless of the heterogeneity suggested by FISH, all the bre akpoints in the AML1 gene were clustered in the same intron between ex ons 5 and 6. Our results bring to over one hundred the number of t(8;2 1) cases in which an identical translocation could be detected at mole cular level by RT-PCR. The high sensitivity of the technique makes it suitable for the diagnosis of this translocation in different stages o f the disease. The impact of the molecular detection of t(8;21) cells in clinical remission as far as the treatment and the management of th e disease are concerned deserves further discussion.