儿童急性淋巴细胞白血病细胞系在适应长春新碱过程中的蛋白质组学变化

Ana Laura Guzmán-Ortiz , Gerardo Aparicio-Ozores , Ricardo Valle-Rios , Oscar Medina-Contreras , Genaro Patiño-López , Héctor Quezada
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引用次数: 0

摘要

墨西哥儿童急性淋巴细胞白血病(ALL)患者的复发发生率约为20%。在这一组中,化疗耐药性可能是最大的挑战之一。通过蛋白质组学研究,可以对药物耐受性等复杂细胞过程进行概述。方法将b系小儿ALL细胞CCRF-SB逐渐暴露于化疗药物长春新碱中,直到6 nM观察到增殖,对照组细胞在不添加长春新碱的情况下培养。利用纳米高效液相色谱(nanoHPLC)和esi离子阱质谱联用分析各组蛋白质组。用PANTHER分类系统将鉴定的蛋白质分成代表性过高的功能类别。结果发现135个蛋白在长春新碱存在下完全表达。最具代表性的功能分类有:Toll受体信号通路、Ras通路、B细胞和T细胞活化、CCKR信号通路、细胞因子介导的信号通路、氧化磷酸化。结论研究表明,白血病细胞对长春新碱的适应过程中,信号转导和线粒体ATP的产生是必不可少的,这些过程是潜在的治疗靶点。
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Proteomic changes in a childhood acute lymphoblastic leukemia cell line during the adaptation to vincristine

Introduction

Relapse occurs in approximately 20% of Mexican patients with childhood acute lymphoblastic leukemia (ALL). In this group, chemoresistance may be one of the biggest challenges. An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies.

Methods

The B-lineage pediatric ALL cell line CCRF-SB was gradually exposed to the chemotherapeutic vincristine until proliferation was observed at 6 nM, control cells were cultured in the absence of vincristine. The proteome from each group was analyzed by nanoHPLC coupled to an ESI-ion trap mass spectrometer. The identified proteins were grouped into overrepresented functional categories with the PANTHER classification system.

Results

We found 135 proteins exclusively expressed in the presence of vincristine. The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation.

Conclusions

Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets.

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