WT1基因在白血病发病及化疗耐药机制中的研究进展
Research progress of WT1 gene in pathogenesis and chemotherapeutic resistance mechanism of leukemia
摘要肾母细胞瘤( WT) 1基因位于人类染色体11p13,其编码的WT1具有抑制肿瘤生长与激活癌基因转录的双重功能,是一个双向转录因子。 WT1基因在各类实体瘤和白血病,尤其急性髓细胞白血病(AML)中高表达。 WT1基因高表达是影响AML患者预后的危险因素,通常提示患者难治或者复发风险高。 WT1基因表达与白血病的发生、发展及患者预后密切相关。但是, WT1基因表达在白血病中的致癌性尚存在争议。一方面, WT1基因表达是致癌因素, WT1基因高表达导致白血病细胞易对化疗耐药,预示患者难治及易耐药、复发;另一方面, WT1基因可能仅在白血病细胞克隆增殖中阶段性表达,而非致癌因素。 WT1基因表达在白血病发病、进展及耐药机制中作用的研究,对于探索白血病的新治疗策略具有重要指导意义。因此,笔者拟就目前 WT1基因表达在白血病发病、进展及化疗耐药机制中作用的研究进展及争议进行综述。
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abstractsWilms tumor ( WT) 1, located on human chromosome 11p13, encodes WT1 with dual functions of inhibiting tumor growth and activating oncogene transcription. It is a bidirectional transcription factor. WT1 gene is highly expressed in various solid tumors and leukemias, especially acute myeloid leukemia (AML). High expressed WT1 gene is a prognostic risk factor of AML patients, which usually indicates high risk of refractory or relapse. Expression of WT1 gene is closely related to occurrence, development and prognosis of leukemia. Nevertheless, carcinogenicity of WT1 gene expression in leukemia remains controversial. On the one hand, WT1 gene expression is a carcinogenic factor. High WT1 gene expression is anti-chemotherapeutic, indicating easy resistance, refractory and high recurrence. On the other hand, WT1 gene expression may only be a phased product of leukemia cell clonal proliferation, not a carcinogenic factor. Research on role of WT1 gene expression in pathogenesis, progression, and resistance mechanisms of leukemia has important guiding significance for exploring new treatment strategies for leukemia. Therefore, this article intends to review and analyze research progress and controversy on role of WT1 gene expression in pathogenesis, progression, and chemotherapeutic resistance mechanisms of leukemia.
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