*Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
†Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
Biosci Rep. 2013 Nov 25;33(6):e00081. doi: 10.1042/BSR20130067.
The hallmark of CML (chronic myeloid leukaemia) is the BCR (breakpoint cluster region)-ABL fusion gene. CML evolves through three phases, based on both clinical and pathological features: a chronic phase, an accelerated phase and blast crisis. TKI (tyrosine kinase inhibitors) are the treatment modality for patients with chronic phase CML. The therapeutic potential of the TKI imatinib is affected by BCR-ABL dependent an independent mechanisms. Development of MDR (multidrug resistance) contributes to the overall clinical resistance. MDR involves overexpression of ABC -transporters (ATP-binding-cassette transporter) among other features. MDR studies include the analysis of cancer cell lines selected for resistance. CML blast crisis is accompanied by increased resistance to apoptosis. This work reviews the role played by the influx transporter OCT1 (organic cation transporter 1), by efflux ABC transporters, molecules involved in the modulation of apoptosis (p53, Bcl-2 family, CD95, IAPs (inhibitors of apoptosis protein)], Hh and Wnt/β-catenin pathways, cytoskeleton abnormalities and other features described in leukaemic cells of clinical samples and CML cell lines. An MDR cell line, Lucena-1, generated from K562 by stepwise exposure to vincristine, was used as our model and some potential anticancer drugs effective against the MDR cell line and patients' samples are presented.
CML（慢性髓性白血病）的标志是 BCR（断裂簇区域）-ABL 融合基因。CML 根据临床和病理特征可分为三个阶段：慢性期、加速期和急变期。TKI（酪氨酸激酶抑制剂）是慢性期 CML 患者的治疗方法。TKI 伊马替尼的治疗潜力受 BCR-ABL 依赖性和非依赖性机制的影响。MDR（多药耐药）的发展导致了整体临床耐药性。MDR 涉及 ABC 转运蛋白（ATP 结合盒转运蛋白）等特征的过度表达。MDR 研究包括对耐药性筛选的癌细胞系的分析。CML 急变期伴随着对细胞凋亡的抵抗力增加。这项工作综述了流入转运体 OCT1（有机阳离子转运体 1）、外排 ABC 转运体、参与细胞凋亡调节的分子（p53、Bcl-2 家族、CD95、IAPs（凋亡蛋白抑制剂）、Hh 和 Wnt/β-catenin 通路、细胞骨架异常和临床样本和 CML 细胞系白血病细胞中描述的其他特征所起的作用。Lucena-1 是从 K562 经逐步暴露于长春新碱产生的 MDR 细胞系，用作我们的模型，并提出了一些针对 MDR 细胞系和患者样本有效的潜在抗癌药物。
