Abstract

Autophagy is an evolutionarily conserved cellular process in which components of the cytoplasm are delivered to lysosomes for degradation and has been proposed to play a role in imatinib resistance in chronic myeloid leukemia cells. Chronic myeloid leukemia is a clonal myeloproliferative disorder arising from the neoplastic transformation of the hematopoietic stem cell. We used a Bcr-Abl-independent and imatinib-resistant K562 subpopulation (K562-IR) that we generated earlier in our laboratory for this study. We showed that in the presence of imatinib autophagy was triggered via LC3I/II transformation, p62 protein expression and acidic vacuoles accumulation in tyrosine kinase inhibitor-sensitive K562 cells; whereas in the cell line K562-IR which is imatinib-resistant and Bcr-Abl independent, autophagy is not triggered. With ongoing research and trails to combine tyrosine kinase inhibitors with autophagy inhibitors, our results suggest a model of resistance in which treatment with a TKI inhibitor does not increase autophagy, basically because its presence does not cause cellular stress due to Bcr-Abl signaling not being required for survival.

中文翻译：

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自噬对伊马替尼耐药的慢性粒细胞白血病细胞系中的 TKI 反应没有贡献

摘要

自噬是一种进化上保守的细胞过程，其中细胞质的成分被递送到溶酶体中进行降解，并被认为在慢性粒细胞白血病细胞的伊马替尼耐药中发挥作用。慢性粒细胞白血病是一种由造血干细胞肿瘤性转化引起的克隆性骨髓增殖性疾病。我们使用了在我们的实验室中较早生成的，不依赖Bcr-Abl且具有伊马替尼抗性的K562亚群（K562-IR）。我们表明，在伊马替尼存在的情况下，自噬是通过 LC3I/II 转化、p62 蛋白表达和酪氨酸激酶抑制剂敏感的 K562 细胞中酸性液泡的积累触发的；而在伊马替尼耐药且不依赖 Bcr-Abl 的细胞系 K562-IR 中，不会触发自噬。