title: Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients.
abstract: BACKGROUND
  Histone deacetylase (HDAC) inhibitors are a novel anti-tumor therapy. To determine whether HDAC inhibitors may be useful in the treatment of adult acute lymphoblastic leukemia (ALL), we examined the acetylation of histone H4 by immunohistochemistry in newly diagnosed ALL patients and evaluated the impact of acetylation on complete remission (CR) rate, relapse-free survival (RFS), and overall survival (OS).
  
  
  METHODS
  Patients > or = 18 years of age and an available diagnostic bone marrow biopsy were evaluated. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, RFS, and OS. The variables histone H4 acetylation (positive or negative), white blood count, cytogenetic (CG) risk group (CALGB criteria), and age were used in multivariate analysis.
  
  
  RESULTS
  On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09). In patients without poor risk CG, there was an impressive association between the presence of histone acetylation and an improved CR rate (OR 3.43, p = 0.035), RFS (HR 0.07, p = 0.005), and OS (HR 0.24, p = 0.007). This association remained statistically significant in multivariate analysis.
  
  
  CONCLUSIONS
  These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL.
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA. advania@ccf.org
authors.forename: Anjali S
authors.initials: AS
authors.lastname: Advani
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gibson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Douglas
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.forename: Xiaoxian
authors.initials: X
authors.lastname: Zhao
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.forename: Ed
authors.initials: E
authors.lastname: Copelan
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.forename: Mikkael
authors.initials: M
authors.lastname: Sekeres
authors.forename: Shawnda
authors.initials: S
authors.lastname: Sungren
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D002478:Cells, Cultured; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D002087:Butyrates; D006657:Histones