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Open Access Research article

Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients

Anjali S Advani1*, Sarah E Gibson2, Elizabeth Douglas2, Tao Jin3, Xiaoxian Zhao2, Matt Kalaycio1, Ed Copelan1, Ronald Sobecks1, Mikkael Sekeres1, Shawnda Sungren1 and Eric D Hsi2

Author Affiliations

1 Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA

2 Clinical Pathology, The Cleveland Clinic, Cleveland, OH, USA

3 Quantitative Health Sciences, The Cleveland Clinic, Cleveland, OH, USA

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BMC Cancer 2010, 10:387  doi:10.1186/1471-2407-10-387

Published: 21 July 2010

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 ≥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.