Breakpoint regions ofETOgene involved in (8; 21) leukemic translocations are enriched in acetylated histone H3

Abstract

One of the most frequent chromosomal translocation found in patients with acute myeloid leukemia (AML) is the t(8;21). This translocation involves the RUNX1 and ETO genes. The breakpoints regions for t(8;21) are located at intron 5 and intron 1 of the RUNX1 and ETO gene respectively. To date, no homologous sequences have been found in these regions to explain their recombination. The breakpoint regions of RUNX1 gene are characterized by the presence of DNasaI hypersensitive sites and topoisomerase II cleavage sites, but no information exists about complementary regions of ETO gene. Here, we report analysis of chromatin structure of ETO breakpoint regions. Chromatin immunoprecipitation (ChIP) were performed with antibodies specific to acetylated histone H3, H4, and total histone H1. Nucleosomal distribution at the ETO locus was evaluated by determining total levels of histone H3. Our data show that in myeloid cells, the breakpoint regions at the ETO gene are enriched in hyperacetylated histone H3 compared to a control region of similar size where no translocations have been described. Moreover, acetylated H4 associates with both the whole ETO breakpoint regions as well as the control intron. Interestingly, we observed no H1 association either at the breakpoint regions or the control region of the ETO gene. Our data indicate that a common chromatin structure enriched in acetylated histones is present in breakpoint regions involved in formation of (8;21) leukemic translocation.

Allogeneic hematopoietic stem cell transplantation for relapsed acute myeloid leukemia in ETO positive with reduced-intensity conditioning

“…But the expression of CD56 + does not refer to the index for the ETO fusion gene positive of patients with AML. It is suggested by the literature that it would be accompanied by its expression and easy to relapse, prognosis for high-risk independent type and hematopoietic stem cell transplantation [ 22 – 23 ] also needs to be conducted. The ETO fusion genes are equipped with a striking feature which is good for disease condition monitoring after transplantation.…”

Clinical, Cytogenetic, and Molecular Findings in Two Cases of Variant t(8;21) Acute Myeloid Leukemia (AML)

“…The t(8;21) is found in ~5–10% of de novo AML and results in the creation of the fusion gene RUNX1-RUNX1T1 (1, 4–6). In most affected individuals, the chromosomal breakpoints are located at intron 5 of the RUNX1 gene and intron 1 of the RUNX1T1 resulting in an in-frame fusion of the N-terminal 177 amino acids of RUNX1 with almost the entire RUNX1T1 protein (7). The RUNT domain from RUNX1, the four nervy homology regions (NHR), and a nuclear localization signal (NLS) from RUNX1T1 are major functional domains of the fusion protein (8, 9).…”