Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with leukemia relapse and leukemia-free survival in adults with B-cell acute lymphoblastic leukemia and normal cytogenetics.
Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with leukemia relapse and leukemia-free survival in adults with B-cell acute lymphoblastic leukemia and normal cytogenetics.
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富含半胱氨酸和甘氨酸的蛋白 2 (CSRP2) 转录水平与 B 细胞急性淋巴细胞白血病和细胞遗传学正常的成人患者的白血病复发和无白血病生存相关。
DOI：
10.18632/oncotarget.16416
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发表时间：
2017-05-30
期刊：
影响因子：
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通讯作者：
Ruan GR
中科院分区：
文献类型：
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作者：
Wang SJ;Wang PZ;Gale RP;Qin YZ;Liu YR;Lai YY;Jiang H;Jiang Q;Zhang XH;Jiang B;Xu LP;Huang XJ;Liu KY;Ruan GR
复发是成人B细胞急性淋巴细胞白血病(ALL)诱导化疗后完全缓解的主要治疗失败原因。更准确地识别可能复发的人是很重要的。我们对转录数据进行了生物信息学分析，以确定在B细胞ALL中异常表达的mRNA。我们选择了9个候选基因进行验证，其中7个基因被证明与B细胞ALL显著相关。接下来我们关注半胱氨酸和富含甘氨酸的蛋白2(CSRP2)的功能和临床相关性。采用实时定量聚合酶链式反应(RT-qPCR)检测236例成人B细胞白血病患者骨髓标本中基因转录水平，并与正常对照进行比较。在236例新诊断的B细胞ALL患者中，有228例(97%)CSRP2过度表达。对168名受试者进行了预后评估。在细胞遗传学正常的患者中，CSRP2转录本水平高的患者5年累计复发率(CIR)和无复发生存率(RFs)较低转录本水平的患者更高(56%[95%可信区间，53，59%]比19%[18，20%]；P=0.011和41%[17，65%]比80%[66-95%]；P=0.007)。在多因素分析中，CSRP2高转录水平与CIR(HR=5.32[1.64~17.28]；P=0.005)和RFS(HR=5.56[1.87，16.53]；P=0.002)独立相关。功能分析表明，CSRP2促进细胞增殖、细胞周期进程、体外集落形成和细胞迁移能力。CSRP2表达异常与化疗耐药有关；下调CSRP2表达可恢复对化疗的敏感性。
Relapse is the major cause of treatment-failure in adults with B-cell acute lymphoblastic leukemia (ALL) achieving complete remission after induction chemotherapy. Greater precision identifying persons likely to relapse is important. We did bio-informatics analyses of transcriptomic data to identify mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate genes for validation 7 of which proved significantly-associated with B-cell ALL. We next focused on function and clinical correlations of the cysteine and glycine-rich protein 2 (CSRP2). Quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine gene transcript levels in bone marrow samples from 236 adults with B-cell ALL compared with samples from normals. CSRP2 was over-expressed in 228 out of 236 adults (97%) with newly-diagnosed B-cell ALL. A prognostic value was assessed in 168 subjects. In subjects with normal cytogenetics those with high CSRP2 transcript levels had a higher 5-year cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels (56% [95% confidence interval, 53, 59%] vs. 19% [18, 20%]; P = 0.011 and 41% [17, 65%] vs. 80% [66–95%]; P = 0.007). In multivariate analyses a high CSRP2 transcript level was independently-associated with CIR (HR = 5.32 [1.64–17.28]; P = 0.005) and RFS (HR = 5.56 [1.87, 16.53]; P = 0.002). Functional analyses indicated CSRP2 promoted cell proliferation, cell-cycle progression, in vitro colony formation and cell migration ability. Abnormal CSRP2 expression was associated with resistance to chemotherapy; sensitivity was restored by down-regulating CSRP2 expression.