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抗凋亡基因survivin在人类白血病中的表达

Expression of the antiapoptosis gene survivin in human leukemia.

作者信息

Mori Ako, Wada Hiroshi, Nishimura Yasuo, Okamoto Takahiro, Takemoto Yoshinobu, Kakishita Eizo

机构信息

Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

出版信息

Int J Hematol. 2002 Feb;75(2):161-5. doi: 10.1007/BF02982021.

DOI:10.1007/BF02982021
PMID:11939262
Abstract

Loss of the inhibition of apoptosis is important in leukemogenesis and may influence the prognosis. Survivin is an inhibitor of apoptosis that shows selective expression during fetal development and in human malignancies. Survivin expression was examined in human leukemias using the reverse transcriptase-polymerase chain reaction. Survivin gene expression was detected in 17 of 31 patients with acute myelocytic leukemia and 11 of 16 patients with acute lymphocytic leukemia but was not identified in normal bone marrow cells. Survivin expression was lower in patients with M3 acute myelocytic leukemia than in patients with other types of acute leukemia. Survivin was not detected in the chronic phase of chronic myelocytic leukemia but was observed in 5 of 7 patients with chronic myelocytic leukemia in blastic crisis. These findings suggest a relationship between survivin gene expression and hematopoietic cell differentiation. In fact, survivin gene expression was down-regulated during the differentiation of HL-60 cells after treatment with dimethyl sulfoxide or all-trans-retinoic acid. Moreover, the disease-free survival rates of patients with survivin expression were lower than in patients without survivin expression. Accordingly, survivin may have a role in leukemogenesis as well as in other malignancies. Detecting survivin may also provide prognostic information.

摘要

凋亡抑制的丧失在白血病发生过程中很重要,并且可能影响预后。生存素是一种凋亡抑制剂,在胎儿发育和人类恶性肿瘤中呈选择性表达。使用逆转录聚合酶链反应检测人类白血病中的生存素表达。在31例急性髓细胞白血病患者中的17例以及16例急性淋巴细胞白血病患者中的11例中检测到生存素基因表达,但在正常骨髓细胞中未检测到。M3型急性髓细胞白血病患者的生存素表达低于其他类型急性白血病患者。在慢性髓细胞白血病的慢性期未检测到生存素,但在7例慢性髓细胞白血病急变期患者中的5例中观察到生存素。这些发现提示生存素基因表达与造血细胞分化之间存在关联。事实上,在用二甲基亚砜或全反式维甲酸处理后,HL-60细胞分化过程中生存素基因表达下调。此外,有生存素表达的患者的无病生存率低于无生存素表达的患者。因此,生存素可能在白血病发生以及其他恶性肿瘤中起作用。检测生存素也可能提供预后信息。

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本文引用的文献

1
High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma.Survivin基因定位于17q25,其高表达与人类神经母细胞瘤的不良预后因素显著相关,并促进细胞存活。
Oncogene. 2000 Feb 3;19(5):617-23. doi: 10.1038/sj.onc.1203358.
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A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers.一种新型抗凋亡基因:生存素信使核糖核酸在非小细胞肺癌中重新表达作为预后标志物
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The inhibitors of apoptosis (IAPs) and their emerging role in cancer.
抗癌3-氟氮杂环丁烷-2-酮的合成、表征及作用机制
Pharmaceuticals (Basel). 2022 Aug 24;15(9):1044. doi: 10.3390/ph15091044.
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Antigen Targets for the Development of Immunotherapies in Leukemia.白血病免疫疗法的抗原靶点。
Int J Mol Sci. 2019 Mar 20;20(6):1397. doi: 10.3390/ijms20061397.
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Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia.鉴定生存素作为成人B细胞急性淋巴细胞白血病免疫治疗的一个有前景的靶点。
Oncotarget. 2017 Dec 17;9(3):3853-3866. doi: 10.18632/oncotarget.23380. eCollection 2018 Jan 9.
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Efficacy of intracellular immune checkpoint-silenced DC vaccine.细胞内免疫检查点沉默的树突状细胞疫苗的疗效。
JCI Insight. 2018 Feb 8;3(3). doi: 10.1172/jci.insight.98368.
7
Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms.内在凋亡途径的失调介导了骨髓增殖性肿瘤中的巨核细胞增生。
J Clin Pathol. 2016 Apr 8;69(11):1017-24. doi: 10.1136/jclinpath-2016-203625.
8
Survivin: A molecular biomarker in cancer.生存素:癌症中的一种分子生物标志物。
Indian J Med Res. 2015 Apr;141(4):389-97. doi: 10.4103/0971-5916.159250.
9
Phase I study of the novel Cdc2/CDK1 and AKT inhibitor terameprocol in patients with advanced leukemias.新型Cdc2/CDK1及AKT抑制剂特拉米普洛用于晚期白血病患者的I期研究。
Invest New Drugs. 2015 Apr;33(2):389-96. doi: 10.1007/s10637-014-0198-y. Epub 2014 Dec 19.
10
The Interface between BCR-ABL-Dependent and -Independent Resistance Signaling Pathways in Chronic Myeloid Leukemia.慢性髓性白血病中BCR-ABL依赖性和非依赖性耐药信号通路之间的界面
Leuk Res Treatment. 2012;2012:671702. doi: 10.1155/2012/671702. Epub 2012 Apr 24.
凋亡抑制蛋白(IAPs)及其在癌症中的新作用。
Oncogene. 1998 Dec 24;17(25):3247-59. doi: 10.1038/sj.onc.1202569.
4
Control of apoptosis and mitotic spindle checkpoint by survivin.生存素对细胞凋亡和有丝分裂纺锤体检查点的调控
Nature. 1998 Dec 10;396(6711):580-4. doi: 10.1038/25141.
5
IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs.IAP家族蛋白存活素可抑制由Fas(CD95)、Bax、半胱天冬酶及抗癌药物诱导的半胱天冬酶活性和细胞凋亡。
Cancer Res. 1998 Dec 1;58(23):5315-20.
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Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer.生存素对细胞凋亡的抑制作用预示着结直肠癌患者的生存率较低。
Cancer Res. 1998 Nov 15;58(22):5071-4.
7
Caspase 2 and caspase 3 protein levels as predictors of survival in acute myelogenous leukemia.半胱天冬酶2和半胱天冬酶3蛋白水平作为急性髓性白血病生存的预测指标
Blood. 1998 Nov 1;92(9):3090-7.
8
Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas.一种新型抗凋亡基因survivin的表达与胃癌中的肿瘤细胞凋亡及p53蓄积相关。
Cancer Res. 1998 May 1;58(9):1808-12.
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Anti-apoptosis gene, survivin, and prognosis of neuroblastoma.抗凋亡基因Survivin与神经母细胞瘤的预后
Lancet. 1998 Mar 21;351(9106):882-3. doi: 10.1016/S0140-6736(05)70294-4.
10
Expression of the Evi-1 gene in haemopoietic cells of children with juvenile myelomonocytic leukaemia and normal donors.Evi-1基因在青少年粒单核细胞白血病患儿及正常供者造血细胞中的表达。
Br J Haematol. 1997 Dec;99(4):882-7. doi: 10.1046/j.1365-2141.1997.4983304.x.