Data di Pubblicazione:
2024
Citazione:
HDAC6 AND HDAC8 IN ACUTE MYELOID LEUKEMIA: LESSONS FROM ZEBRAFISH / A. Pezzotta. ((Intervento presentato al convegno Biometra seminars tenutosi a Italia nel 2024.
Abstract:
Aberrant expression and activity of epigenetic modifiers belonging to the histone
deacetylase (HDAC) family have been reported in patients with acute myeloid leukemia
(AML). The zebrafish model, in which the mechanisms involved in hematopoiesis are
conserved with those of higher vertebrates, represents an ideal tool for studying the role
of the different HDAC in leukemia. Using transgenic embryos with green-labeled
hematopoietic stem and progenitor cells (HSPCs), we demonstrated that HDAC6 and
HDAC8 overexpression leads to an increase in the HSPCs population. This phenotype,
which resembles a pre-AML state, was reversed by treating the embryos with selective
HDAC6 (TubastatinA) and HDAC8 (PCI-34051) inhibitors. Searching for the molecular
mechanisms underlining the hematopoietic phenotype, we found that HDAC8 and
HDAC6 promote the pre-AML phenotype acting on Wnt and Hh signaling pathways. The
new frontier in the management of AML patients is represented by combination
treatments and we showed that HDAC6- and HDAC8-specific inhibitors can be used in
these settings together with chemotherapic agents. We showed that TubastatinA and
PCI-34051 synergize with cytarabine to suppress the leukemic phenotype of two AML
zebrafish models and reduce the viability of AML cell lines. In summary, using the zebrafish
model, we demonstrated the efficacy of TubastatinA and PCI-34051, which could be
exploited also for the treatment of tumors carrying HDAC6 and HDAC8 overexpression
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
zebrafish; AML; HDAC
Elenco autori:
A. Pezzotta
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