Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia ALL patientsReport as inadecuate




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BMC Cancer

, 10:387

First Online: 21 July 2010Received: 07 January 2010Accepted: 21 July 2010DOI: 10.1186-1471-2407-10-387

Cite this article as: Advani, A.S., Gibson, S.E., Douglas, E. et al. BMC Cancer 2010 10: 387. doi:10.1186-1471-2407-10-387

Abstract

BackgroundHistone 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.

MethodsPatients ≥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.

ResultsOn 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.

ConclusionsThese data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL.

List Of AbbreviationsHDACHistone deacetylase

ALLAcute lymphoblastic leukemia

CRComplete remission

OSOverall survival

CGCytogenetic

CALGBCancer and Leukemia Group B

RFSRelapse-free survival

OROdds ratio

HRHazard ratio

CIConfidence interval

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-387 contains supplementary material, which is available to authorized users.

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Author: Anjali S Advani - Sarah E Gibson - Elizabeth Douglas - Tao Jin - Xiaoxian Zhao - Matt Kalaycio - Ed Copelan - Ronald Sob

Source: https://link.springer.com/







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