title: Polyclonal haemopoieses associated with long-term persistence of the AML1-ETO transcript in patients with FAB M2 acute myeloid leukaemia in continous clinical remission.
abstract: The t(8;21) (q22;q22) translocation is a recurring chromosomal abnormality observed in about 20-40% 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%). 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.
authors.affiliation: Dipartimento di Scienze Biomediche ed Oncologia Umana, CNR-CIOS, Ospedale S. Luigi Gonzaga, Università di Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Guerrasio
authors.forename: C
authors.initials: C
authors.lastname: Rosso
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: F
authors.initials: F
authors.lastname: Lo Coco
authors.forename: M
authors.initials: M
authors.lastname: Pampinella
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: C
authors.initials: C
authors.lastname: Lanza
authors.forename: B
authors.initials: B
authors.lastname: Allione
authors.forename: L
authors.initials: L
authors.lastname: Resegotti
authors.forename: G
authors.initials: G
authors.lastname: Saglio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000096:biosynthesis*; D014178:Translocation, Genetic
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors