Polyclonal haemopoieses associated with long-term persistence of the AML1-ETO transcript in patients with FAB M2 acute myeloid leukaemia in continuous clinical remission

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Abstract

Summary

The t(8;21) (q22;q22) translocation is a recurring chromosomal abnormality observed in about 20-40 percent of AML patients with subtype FAB M2 (AML-M2). The molecular facet of this translocation is represented by the formation of a new hybrid gene, the AML1-ETO, which is regularly transcribed in a chimaeric mRNA and translated into a new fusion protein believed 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 Institutions. A hybrid transcript was detected in 11 cases (23 percent). Minimal residual disease status was investigated in three patients in continuous complete remission (CCR) after a median follow-up of 44 months; at least one sample from each subject was found positive for the AML1-ETO transcript suggesting a long-term persistence of t(8;21) leukaemic cells.

In two female patients in CCR a `clonality' analysis was performed on peripheral blood DNA by exploiting the X chromosome inactivation pattern of the human androgen-receptor gene (HUMARA); in both cases the results were consistent with the presence of a polyclonal haemopoiesis.

Our data confirm that the persistence of residual cells expressing 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 sustained by a polyclonal bone marrow reconstitution.

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