Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients.
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.
Advani
Anjali S
AS
Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA. advania@ccf.org
Gibson
Sarah E
SE
Douglas
Elizabeth
E
Jin
Tao
T
Zhao
Xiaoxian
X
Kalaycio
Matt
M
Copelan
Ed
E
Sobecks
Ronald
R
Sekeres
Mikkael
M
Sungren
Shawnda
S
Hsi
Eric D
ED
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
D002087:Butyrates; D006657:Histones