Journal
LEUKEMIA RESEARCH
Volume 39, Issue 12, Pages 1455-1461Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2015.10.006
Keywords
Acute lymphoblastic leukemia; Epigenetics; Histone acetylation
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Funding
- National Center of Research and Development (NCBiR) [LIDER 031/635/1-5/13/NCBR/2014]
- Polpharma Scientific Foundation [4/19/IX/1]
- National Center of Science [2011/03/B/NZ5/05906, N N407 254440]
- Lodz Medical University [502-03/1-038-01/502-14-212]
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Epigenetic dysregulation is a hallmark of cancer executed by a number of complex processes the most important of which converge on DNA methylation and histone protein modifications. Epigenetic marks are potentially reversible and thus promising drug targets. In the setting of acute lymphoblastic leukemia (ALL) they have been associated with clinicopathological features including risk of relapse or molecular subgroups of the disease. Here, using immunocytochemistry of bone marrow smears from diagnosis, we studied global histone H4 acetylation, whose loss was previously linked to treatment failure in adults with ALL, in pediatric patients. We demonstrate that preserved global histone H4 acetylation is significantly associated with favorable outcome (RFS, EFS, OS) in children with B cell progenitor (BCP) ALL, recapitulating the findings from adult populations. Further, for the first time we demonstrate differential histone H4 acetylation in molecular subclasses of BCP-ALL including cases with ETV6-RUNX1 fusion gene or PAX5 deletion or deletions in genes linked to B cell development. We conclude global histone H4 acetylation is a prognostic marker and a potential therapeutic target in ALL. (C) 2015 Elsevier Ltd. All rights reserved.
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