Sung Ki Woong, Choi Jaewon, Hwang Yu Kyeong, Lee Sang Jin, Kim Hee-Jin, Lee Soo Hyun, Yoo Keon Hee, Jung Hye Lim, Koo Hong Hoe
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Clin Cancer Res. 2007 Sep 1;13(17):5109-14. doi: 10.1158/1078-0432.CCR-07-0693.
The genes that encode inhibitor of apoptosis proteins are frequently overexpressed in human cancers and can be associated with resistance to therapy. The overexpression of Apollon, a member of inhibitor of apoptosis proteins, is intuitively expected to be associated with unfavorable clinical features in malignant diseases; however, there have been no clinical studies reporting the prognostic relevance of Apollon expression in human malignancies. This study was done to investigate the clinical relevance of the expression of Apollon in childhood de novo acute myeloid leukemia.
In 55 pediatric patients with de novo acute myeloid leukemia, the level of Apollon expression was determined by using quantitative reverse transcriptase-PCR and was analyzed with respect to the patients' clinical features and treatment outcomes.
Apollon expression was found to be higher in patients with a leukocyte number of >or=10,000/microL, patients with extramedullary disease, and patients with the French-American-British classification subtype M7. In addition, Apollon overexpression (>or=median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a poorer 3-year relapse-free survival rate (48.3 +/- 11.2% versus 78.7 +/- 8.5%, P = 0.040).
This is the first study demonstrating the prognostic implication of the Apollon expression in human cancers, indicating that Apollon overexpression may be used as a poor prognostic marker in childhood acute myeloid leukemia through validation by further studies.
编码凋亡抑制蛋白的基因在人类癌症中经常过度表达,并可能与治疗耐药性相关。凋亡抑制蛋白家族成员Apollon的过度表达直观上被认为与恶性疾病中不良的临床特征相关;然而,尚无临床研究报道Apollon表达在人类恶性肿瘤中的预后相关性。本研究旨在探讨Apollon表达在儿童初发急性髓系白血病中的临床相关性。
在55例儿童初发急性髓系白血病患者中,采用定量逆转录聚合酶链反应测定Apollon表达水平,并分析其与患者临床特征及治疗结果的关系。
发现白细胞计数≥10,000/μL的患者、有髓外疾病的患者以及法国-美国-英国分类亚型M7的患者中Apollon表达较高。此外,Apollon过表达(≥中位表达)与诱导化疗第7天的不良反应相关,也与较差的3年无复发生存率相关(48.3±11.2%对78.7±8.5%,P = 0.040)。
这是第一项证明Apollon表达在人类癌症中具有预后意义的研究,表明通过进一步研究验证,Apollon过表达可能作为儿童急性髓系白血病不良预后的标志物。