通过免疫组织化学检测新诊断的成人急性淋巴细胞白血病（ALL）患者的组蛋白 H4 乙酰化与预后的关系。

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

机构信息

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

出版信息

BMC Cancer. 2010 Jul 21;10:387. doi: 10.1186/1471-2407-10-387.

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.

背景

组蛋白去乙酰化酶（HDAC）抑制剂是一种新型的抗肿瘤疗法。为了确定 HDAC 抑制剂是否可用于治疗成人急性淋巴细胞白血病（ALL），我们通过免疫组织化学方法检测了新诊断的 ALL 患者中组蛋白 H4 的乙酰化，并评估了乙酰化对完全缓解（CR）率、无复发生存（RFS）和总生存（OS）的影响。

方法

评估了年龄≥18 岁且有可用的诊断性骨髓活检的患者。采用 Cox 比例风险分析确定 CR、RFS 和 OS 的单变量和多变量相关性。将组蛋白 H4 乙酰化（阳性或阴性）、白细胞计数、细胞遗传学（CG）风险组（CALGB 标准）和年龄等变量用于多变量分析。

结果

多变量分析显示，组蛋白乙酰化与 OS 改善趋势相关（所有 CG 风险组）（HR=0.51，p=0.09）。在没有不良 CG 风险的患者中，组蛋白乙酰化的存在与 CR 率（OR=3.43，p=0.035）、RFS（HR=0.07，p=0.005）和 OS（HR=0.24，p=0.007）的改善之间存在显著关联。在多变量分析中，这种关联仍然具有统计学意义。