POLYCLONAL HAEMOPOIESES ASSOCIATED WITH LONG-TERM PERSISTENCE OF THE AML1-ETO TRANSCRIPT IN PATIENTS WITH FAB M2 ACUTE MYELOID-LEUKEMIA IN CONTINUOUS CLINICAL REMISSION

The t(8;21) (q22;q22) translocation is recurring chromosomal abnormali ty observed in about 20-40% of AML patients with subtype FAB M2 (AML-M 2). The molecular facet of this translocation is represented by the fo rmation of a new hybrid gene, the AML1-ETO, which is regularly transcr ibed in a chimaeric mRNA and translated into a new fusion protein beli eved to have a key role in the pathogenesis of this type of leukaemia. We looked for the presence of AML1-ETO transcripts, by RT-PCR, in 49 unselected patients affected by AML-M2 diagnosed at various Italian In stitutions. A hybrid transcript was detected in 11 cases (23%). Minima l residual disease status was investigated in three patients in contin uous complete remission (CCR) after a median follow-up of 44 months; a t least one sample from each subject was found positive for the AML1-E TO transcript suggesting a long-term persistence of t(8;21) leukaemic cells. In two female patients in CCR a 'clonality' analysis was perfor med on peripheral blood DNA by exploiting the X chromosome inactivatio n pattern of the human androgen-receptor gene (HUMARA); in both cases the results were consistent with the presence of a polyclonal haemopoi esis. Our data confirm that the persistence of residual cells expressi ng the AML1-ETO transcripts is a frequent occurrence even in patients with long-term remission; on the other hand, clonality assays indicate that in t(8;21) leukaemias long-term remission haemopoiesis is sustai ned by a polyclonal bone marrow reconstitution.