title: 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.
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.
authors.affiliation: Department of Nephropathology, Medical University of Lodz, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Janczar
authors.affiliation: Department of Paediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland. Electronic address: szymon.janczar@umed.lodz.pl.
authors.forename: S
authors.initials: S
authors.lastname: Janczar
authors.affiliation: Department of Paediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Pastorczak
authors.affiliation: Department of Paediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Mycko
authors.affiliation: Department of Life Science, University of Bedfordshire, UK.
authors.forename: A J W
authors.initials: AJ
authors.lastname: Paige
authors.affiliation: Department of Paediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Zalewska-Szewczyk
authors.affiliation: Department of Nephropathology, Medical University of Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Wagrowska-Danilewicz
authors.affiliation: Department of Nephropathology, Medical University of Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Danilewicz
authors.affiliation: Department of Paediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit / Q000502:physiology*; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D051757:PAX5 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011499:Protein Processing, Post-Translational; D012074:Remission Induction; D014178:Translocation, Genetic; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D006657:Histones; D015514:Oncogene Proteins, Fusion; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein
keywords: Acute lymphoblastic leukemia; Epigenetics; Histone acetylation