Epigenetic regulation of cathepsin L expression in chronic myeloid leukaemia.
Epigenetic regulation of cathepsin L expression in chronic myeloid leukaemia.
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慢性髓样白血病中组织蛋白酶L表达的表观遗传调节。
DOI：
10.1111/j.1582-4934.2010.01203.x
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发表时间：
2011-10
影响因子：
5.3
通讯作者：
Chauhan SS
中科院分区：
文献类型：
--
作者：
Samaiya M;Bakhshi S;Shukla AA;Kumar L;Chauhan SS
组织蛋白酶 L (CTSL) 在实体瘤中的表达和意义已得到广泛研究。然而，目前还没有关于慢性粒细胞白血病（CML）的此类信息。我们研究了 47 名成年 CML 患者的外周血单核细胞 (PBMC) 中这种蛋白酶的活性和表达。 30名患有全身性疾病的成年人和50名健康志愿者作为对照。通过实时 qPCR 定量 CTSL、其特异性内源性抑制剂半胱氨酸蛋白酶抑制剂 C 和转录上调因子血管内皮生长因子 (VEGF) 的 mRNA 水平。与 CML 加速期/急变期 (AP/BC) 患者和对照相比，CML 慢性期 (CP) 患者的 CTSL 蛋白酶活性及其 mRNA 表达显着升高 (P≤ 0.001)。 VEGF在CP中表达最明显，在恶性肿瘤晚期表达下降（P≤0.001），与CTSL表达呈强正相关（r=0.97；P≤0.001）。 CML 中胱抑素 C 的表达显着较低（P≤0.001），并且与 CTSL 活性呈负相关（r=-0.713；P≤0.001）。与 CML AP/BC 患者以及对照相比，CML CP 中的 CTSL 启动子显着低甲基化。 K562 是一种 BC CML 细胞系，其 CTSL 活性、表达和 CTSL 启动子甲基化状态与 CML AP/BC 患者相当。用 5'-氮杂胞苷处理从 CML AP/BC 患者分离的这些细胞或 PBMC 导致 CSTL 活性和/或表达显着增加，从而证明了启动子甲基化在 CML 中 CTSL 阶段特异性表达中的作用。 CTSL 在恶性肿瘤不同阶段的 CML 中的差异表达可能有助于识别高危患者，从而促进更好的疾病管理。
The expression and significance of cathepsin L (CTSL) has been extensively studied in solid tumours. However no such information in chronic myeloid leukaemia (CML) was available. We investigated the activity and expression of this protease in peripheral blood mononuclear cells (PBMCs) of 47 adult CML patients. Thirty adults suffering from systemic diseases and 50 healthy volunteers served as controls. The mRNA levels of CTSL, its specific endogenous inhibitor cystatin C and transcriptional up-regulator vascular endothelial growth factor (VEGF) were quantitated by real-time qPCR. CTSL protease activity and its mRNA expression were significantly higher in CML chronic phase (CP) patients compared to CML accelerated phase/blast crisis (AP/BC) patients and controls (P≤ 0.001). VEGF whose expression was most pronounced in CP and declined (P≤ 0.001) in the advanced phases of the malignancy exhibited a strong positive correlation with CTSL expression (r= 0.97; P≤ 0.001). Cystatin C expression was significantly lower (P≤ 0.001) in CML and displayed inverse correlation with CTSL (r=−0.713; P≤ 0.001) activity. CTSL promoter was significantly hypomethylated in CML CP compared to CML AP/BC patients as well as controls. K562, a BC CML cell line displayed CTSL activity, expression and methylation status of CTSL promoter that was comparable to CML AP/BC patients. Treatment of these cells or PBMCs isolated from CML AP/BC patients with 5′-aza-cytidine resulted in a dramatic increase in CSTL activity and/or expression thereby demonstrating the role of promoter methylation in the stage specific expression of CTSL in CML. Differential expression of CTSL in CML at various stages of malignancy may prove useful in identification of the high-risk patients thereby facilitating better management of disease.
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影响因子：
6.4
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通讯作者：
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