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- W2810667066 abstract "Introduction Aneuploidy, the presence of an abnormal number of chromosomes within a cell, is a recurrent characteristic of both solid and haematological tumours. A substantial number of patients with acute myeloid leukaemia (AML) harbour a complex karyotype, which consists in three or more aberrations, including numerical chromosome abnormalities in the absence of prognostically favourable rearrangements. The prognosis of these patients is dismal due to the poor response to the conventional therapy, a combination of the nucleoside analogue cytarabine and the anthracycline daunorubicin. For this reason compounds that specifically cause lethality in karyotypically abnormal cells with numerical chromosome aberrations could provide a novel treatment approach. Material and methods With the aim to identify compounds that are more cytotoxic against aneuploid versus diploid AML cells, we tested a group of chemicals on 36 primary human AML samples (18 with a euploid karyotype, 18 with an aneuploid karyotype) derived from either bone marrow or peripheral blood. We further established an isogenic AML cell line model to confirm the observations made on primary cells and to gain insight into the aneuploidy-specific mechanisms of action of the drugs. Results and discussions We identified 8-azaguanine as a compound that causes lethality in aneuploid primary cells more efficiently than in euploid cells. In the cell line model, both viability and apoptosis assays suggest that the aneuploid clones at earlier differentiation levels respond better to 8-azaguanine than the euploid cells, with the tetraploid clone responding the best. Conclusion Our results provide an initial clue to proceed with further investigations on the therapeutic application of 8-azaguanine against aneuploid AML." @default.
- W2810667066 created "2018-07-10" @default.
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- W2810667066 date "2018-06-01" @default.
- W2810667066 modified "2023-09-26" @default.
- W2810667066 title "PO-457 Is 8-azaguanine selectively active against aneuploid acute myeloid leukaemia?" @default.
- W2810667066 doi "https://doi.org/10.1136/esmoopen-2018-eacr25.478" @default.
- W2810667066 hasPublicationYear "2018" @default.
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