Phosphorylated CXCR4 Is Associated With Poor Survival in Adults With B-Acute Lymphoblastic Leukemia
Phosphorylated CXCR4 Is Associated With Poor Survival in Adults With B-Acute Lymphoblastic Leukemia
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DOI：
10.1002/cncr.26113
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发表时间：
2011-10-15
期刊：
影响因子：
6.2
通讯作者：
Konopleva, Marina
中科院分区：
文献类型：
--
作者：
Konoplev, Sergej;Jorgensen, Jeffrey L.;Konopleva, Marina
背景技术背景：CXC趋化因子受体4（CXCR 4）通过磷酸化（pCXCR 4）活化，并且对于造血前体向骨髓的迁移是必需的。CXCR 4过表达预示急性髓系白血病患者预后不良关于CXCR 4对B急性淋巴细胞白血病（B-ALL）患者预后影响的数据很少，且仅限于儿科人群。方法：分析54例初治成人B-ALL患者CXCR 4和pCXCR 4的表达情况。使用抗CXCR 4抗体通过流式细胞术（FC）和免疫组织化学（IHC）评估CXCR 4。使用抗pCXCR 4抗体评估pCXCR 4表达。结果：研究组包括30名男性和24名女性，中位年龄为42岁（范围，17-84岁）。费城染色体阳性19例。中位随访时间为16个月（范围：17-84个月）。49名患者完全缓解，12名患者复发，中位无复发生存期>120周。15名患者（28%）死亡，中位生存期>125周。FC和IHC检测的CXCR 4高度相关（P <0.001）。CXCR 4与临床或实验室检查结果或生存率无关。相比之下，pCXCR 4与较高的白细胞计数（P = .006）和血清胆红素水平（P = .03）相关。在多变量分析中，pCXCR 4表达（P = 0.027）、高血清肌酐水平（P <0.01）、费城染色体的存在（P = 0.017）和晚期临床反应（P <0.001）与总生存率较差相关。结论：目前的结果表明，检测CXCR 4的活化形式，pCXCR 4，提供独立的预后信息，在成人患者的B-ALL。Cancer 2011;117：4689-95. (C)2011年美国癌症协会
BACKGROUND: CXC chemokine receptor 4 (CXCR4) is activated by phosphorylation (pCXCR4) and is essential for the migration of hematopoietic precursors to bone marrow. CXCR4 overexpression predicts a poor prognosis in patients with acute myeloid leukemia. Data regarding the prognostic impact of CXCR4 in patients with B-acute lymphoblastic leukemia (B-ALL) are sparse and limited to the pediatric population. METHODS: The authors analyzed CXCR4 and pCXCR4 expression in 54 adults with newly diagnosed B-ALL. CXCR4 was assessed by flow cytometry (FC) and immunohistochemistry (IHC) using an anti-CXCR4 antibody. pCXCR4 expression was assessed using an anti-pCXCR4 antibody. RESULTS: The study group included 30 men and 24 women with a median age of 42 years (range, 17-84 years). Philadelphia chromosome was present in 19 patients. The median follow-up was 16 months (range, 17-84 months). Forty-nine patients had a complete response, and 12 patients relapsed with a median relapse free survival >120 weeks. Fifteen patients (28%) died with a median survival >125 weeks. CXCR4 detected by FC and IHC was highly correlated (P < .001). CXCR4 was not associated with clinical or laboratory findings or survival. In contrast, pCXCR4 was associated with higher leukocyte count (P = .006) and serum bilirubin level (P = .03). In multivariate analysis, pCXCR4 expression (P = .027), high serum creatinine level (P < .01), presence of the Philadelphia chromosome (P = .017), and late clinical response (P < .001) were associated with worse overall survival. CONCLUSIONS: The current results indicated that detection of the activated form of CXCR4, pCXCR4, provides independent prognostic information in adult patients with B-ALL. Cancer 2011;117:4689-95. (C) 2011 American Cancer Society.