The Prognostic Value of CXCR4 in Acute Myeloid Leukemia
The Prognostic Value of CXCR4 in Acute Myeloid Leukemia
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DOI：
10.1097/pai.0b013e3182606f4d
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发表时间：
2013-01-01
影响因子：
1.6
通讯作者：
Arber, Daniel A.
中科院分区：
文献类型：
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作者：
Ahn, Jeong Yeal;Seo, Katie;Arber, Daniel A.
背景：CXC 趋化因子受体 (CXCR4) 已被证明在急性髓系白血病 (AML) 患者的亚群中表达，并且与不良预后相关。 CXCR4 表达似乎是异质性 AML 患者生存的独立预后因素。为了更好地评估其意义，我们分析了一组 AML 患者中 CXCR4 的表达。方法：分析了 2003 年至 2008 年间 53 例 AML 患者中 CXCR4 表达的预后价值。福尔马林固定、石蜡包埋的骨髓活检或血块切片采用免疫组化方法染色。结果：CXCR4在26例患者中表达（49.1%）。患者年龄小于 60 岁 (P = 0.023)、诱导治疗后达到完全缓解 (P < 0.001) 和无 CXCR4 表达 (P = 0.010) 均与更好的无进展生存期 (PFS) 相关。在 NPMI、CEBPA、FLT3 ITD 和 FLT3 D835 突变以及 CXCR4 表达中，只有 CXCR4 表达与 PFS 相关（P = 0.010；通过对数秩检验）。通过多变量分析，CXCR4 表达是一个独立的预后因素（PFS 为 P = 0.001，总生存期为 P = 0.001）。 22例患者中有15例检测到CXCR4表达正常核型患者（68.2%，相对比4.46，P=0.035）。正常核型 AML 中 CXCR4 的表达显示较差的 PFS（中位 2.0 对比 10.7 个月，P = 0.026），并且有较差的总体生存趋势（中位 10.8 对比 14.0 个月，P = 0.058）。结论：这些结果表明 CXCR4 表达与 AML 患者的不良预后相关。具体来说，CXCR4 表达在正常核型 AML 中很常见，并且是该人群中更具侵袭性疾病的标志。 CXCR4表达可以纳入AML患者的风险评估。
Background: CXC chemokine receptor (CXCR4) has been shown to be expressed in a subset of acute myeloid leukemia (AML) patients and is correlated with a poor prognosis. CXCR4 expression appears to be an independent prognostic factor for survival in a heterogeneous group of AML patients. To better assess its significance, we analyzed CXCR4 expression in a group of AML patients.Methods: The prognostic value of CXCR4 expression in 53 patients with AML presenting between 2003 and 2008 was analyzed. Forma lin-fixed, paraffin-embedded bone marrow biopsy or clot sections were stained using immunohistochemical methods.Results: CXCR4 was expressed in 26 patients (49.1%). A patient age of less than 60 years (P = 0.023), achievement of complete remission after induction therapy (P < 0.001), and no CXCR4 expression (P = 0.010) were all associated with better progression-free survival (PFS). Among mutations of NPMI, CEBPA, FLT3 ITD, and FLT3 D835 and expression of CXCR4, only CXCR4 expression was associated with PFS (P = 0.010; by log-rank test). By multivariate analysis, CXCR4 expression was an independent prognostic factor (P = 0.001 for PFS and P = 0.001 for overall survival). CXCR4 expression in patients with a normal karyotype was detected in 15 of 22 patients (68.2%, relative ratio 4.46, P = 0.035). Expression of CXCR4 in normal-karyotype AML showed inferior PFS (median 2.0 vs. 10.7 mo, P = 0.026) and had a trend toward inferior overall survival (median 10.8 vs. 14.0 mo, P = 0.058).Conclusions: These results suggest that CXCR4 expression is associated with poor prognosis in patients with AML. Specifically, CXCR4 expression is common in normal-karyotype AML and is a marker of more aggressive disease in this population. CXCR4 expression could be incorporated into the risk assessment of patients with AML.