Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer Rio de Janeiro, RJ, Brazil.
Oncol Rep. 2011 Aug;26(2):471-8. doi: 10.3892/or.2011.1296. Epub 2011 May 4.
Resistance to tyrosine-kinase inhibitors is a serious problem in the treatment of chronic myeloid leukemia (CML). Using Western blot, real-time qRT-PCR and flow cytometry, we investigated the expression of survivin, Smac/DIABLO and P-glycoprotein (Pgp) in patients with CML. Survivin overexpression has been associated with cancer progression, multidrug resistance, poor prognosis and short survival in several types of neoplasms including hematological malignancies. In this work, survivin expression was significantly elevated in late, in contrast to early, chronic phase CML (p=0.044). Patients with high or intermediate prognostic Sokal score presented higher survivin levels (p=0.012), as well as Smac/DIABLO levels (p=0.009) compared to low Sokal score. The strong correlation between survivin and Pgp expression in late (p=0.018), but not in early (p=0.5) chronic phase of CML, suggests that this association may play a biological role in late CML phase and may offer an important target for the development of new therapies.
酪氨酸激酶抑制剂耐药是慢性髓性白血病(CML)治疗中的一个严重问题。我们使用 Western blot、实时 qRT-PCR 和流式细胞术研究了 CML 患者中生存素、Smac/DIABLO 和 P-糖蛋白(Pgp)的表达。在包括血液恶性肿瘤在内的几种类型的肿瘤中,生存素的过度表达与癌症进展、多药耐药、不良预后和短生存期相关。在这项工作中,与早期慢性期 CML 相比,晚期慢性期 CML 中生存素的表达显著升高(p=0.044)。高或中预后 Sokal 评分的患者表现出更高的生存素水平(p=0.012),以及 Smac/DIABLO 水平(p=0.009)高于低 Sokal 评分。在晚期(p=0.018)而非早期(p=0.5)慢性期 CML 中生存素与 Pgp 表达之间的强烈相关性表明,这种相关性可能在晚期 CML 阶段发挥生物学作用,并可能为新疗法的开发提供重要靶标。