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生存素与Aven:急性白血病中两种不同的抗凋亡信号

Survivin and aven: two distinct antiapoptotic signals in acute leukemias.

作者信息

Paydas S, Tanriverdi K, Yavuz S, Disel U, Sahin B, Burgut R

机构信息

Department of Oncology, Cukurova University Faculty of Medicine, Adana, Turkey.

出版信息

Ann Oncol. 2003 Jul;14(7):1045-50. doi: 10.1093/annonc/mdg277.

DOI:10.1093/annonc/mdg277
PMID:12853345
Abstract

BACKGROUND

Antiapoptotic signals are important in the development, progression and prognosis of malignant tumors. The aim of this study was to determine the two distinct antiapoptotic signals-survivin and aven-in acute leukemias and compare them with clinical and hematological findings and response to therapy. Real-time quantitative PCR was used and survivin and aven were detected at the messenger (m)RNA level.

PATIENTS AND METHODS

Sixty-five patients with acute leukemia [37 with acute myeloblastic leukemia (AML) and 28 with acute lymphoblastic leukemia (ALL)] were used as the study group and 10 healthy subjects were used as the control group.

RESULTS

Survivin was between 0.0 and 0.829 copy number/cell (median 0.0721, mean 0.5424301909 +/- 0.139799488589) and aven was between 0.0 and 0.853 copy number/cell (median 0.0124, mean 0.070335542 +/- 0.1524685709). We found an important association between survivin and aven (P = 0.000). Both survivin and aven were higher in the study group than in the controls (P = 0.001 and 0.035, respectively). When we compared survivin and aven with other clinical and hematological parameters, there was an important association between survivin and extramedullary involvement (P = 0.033), survivin and alkaline phosphatase (P = 0.06), white blood cell (WBC) count and lactate dehydrogenase (LDH) (P = 0.000), WBC count and uric acid (P = 0.074), hemoglobin level and LDH (P = 0.072), LDH and uric acid (P = 0.057), CD7 expression and survivin (P = 0.097), and CD34 expression and aven (P = 0.058). Response to therapy was evaluated according to the survivin and aven levels. Survivin level was lower in refractory patients as compared with complete responders (P = 0.085). Aven level was higher in patients with relapse as compared with non-relapse patients (P = 0.04). There was no important association between survivin or aven and performance status, lymphadenopathy or organomegaly.

CONCLUSIONS

Both survivin and aven are important antiapoptotic signals in acute leukemias, and the association between extramedullary involvement, CD7 expression and CD34 expression, which are important poor prognostic indicators in acute leukemias, suggests that survivin and/or aven may be novel prognostic indicators in acute leukemias. Further studies with a higher number of patients will be more informative.

摘要

背景

抗凋亡信号在恶性肿瘤的发生、发展及预后中具有重要作用。本研究旨在确定急性白血病中两种不同的抗凋亡信号——生存素(survivin)和Aven,并将它们与临床及血液学表现以及对治疗的反应进行比较。采用实时定量聚合酶链反应(PCR),在信使核糖核酸(mRNA)水平检测生存素和Aven。

患者与方法

65例急性白血病患者[37例急性髓系白血病(AML)和28例急性淋巴细胞白血病(ALL)]作为研究组,10例健康受试者作为对照组。

结果

生存素拷贝数/细胞介于0.0至0.829之间(中位数0.0721,均值0.5424301909±0.139799488589),Aven拷贝数/细胞介于0.0至0.853之间(中位数0.0124,均值0.070335542±0.1524685709)。我们发现生存素与Aven之间存在重要关联(P = 0.000)。研究组中生存素和Aven均高于对照组(分别为P = 0.001和P = 0.035)。当我们将生存素和Aven与其他临床及血液学参数进行比较时,生存素与髓外浸润之间存在重要关联(P = 0.033),生存素与碱性磷酸酶之间存在关联(P = 0.06),白细胞(WBC)计数与乳酸脱氢酶(LDH)之间存在关联(P = 0.000),WBC计数与尿酸之间存在关联(P = 0.074),血红蛋白水平与LDH之间存在关联(P = 0.072),LDH与尿酸之间存在关联(P = 0.057),CD7表达与生存素之间存在关联(P = 0.097),CD34表达与Aven之间存在关联(P = 0.058)。根据生存素和Aven水平评估对治疗的反应。难治性患者的生存素水平低于完全缓解者(P = 0.085)。复发患者的Aven水平高于未复发患者(P = 0.04)。生存素或Aven与体能状态、淋巴结病或器官肿大之间无重要关联。

结论

生存素和Aven均是急性白血病中重要的抗凋亡信号,而髓外浸润、CD7表达和CD34表达是急性白血病重要的不良预后指标,它们之间的关联表明生存素和/或Aven可能是急性白血病新的预后指标。纳入更多患者的进一步研究将提供更多信息。

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