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    Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia.

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    Authors
    Janczar, Karolina
    Janczar, Szymon
    Pastorczak, Agata
    Mycko, K.
    Paige, Adam J.W.
    Zalewska-Szewczyk, Beata
    Wagrowska-Danilewicz, M.
    Danilewicz, Marian
    Mlynarski, Wojciech
    Affiliation
    Medical University of Lodz
    University of Bedfordshire
    Issue Date
    2015-10-20
    Subjects
    acute lymphoblastic leukemia
    epigenetics
    histone acetylation
    leukaemia
    
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    Abstract
    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.
    Citation
    Janczar, K., Janczar, S., Pastorczak, K., Mycko, K., Paige, A.J.W., Zalewska-Szewczyk, Wagrowska-Danilewicz, M., Mlynarski, W. (2015) ' Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia' Leukemia Research 39 (12) 1455-1461
    Publisher
    Elsevier
    Journal
    Leukemia research
    URI
    http://hdl.handle.net/10547/581937
    DOI
    10.1016/j.leukres.2015.10.006
    PubMed ID
    26520622
    Additional Links
    http://www.sciencedirect.com/science/article/pii/S0145212615305312
    http://www.ncbi.nlm.nih.gov/pubmed/26520622
    Type
    Article
    Language
    en
    ISSN
    1873-5835
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.leukres.2015.10.006
    Scopus Count
    Collections
    Biomedical Science

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