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Defined, serum/feeder-free conditions for expansion and drug screening of primary B-acute lymphoblastic leukemia

Functional screening for compounds represents a major hurdle in the development of rational therapeutics for B-acute lymphoblastic leukemia (B-ALL). In addition, using cell lines as valid models for evaluating responses to novel drug therapies raises serious concerns, as cell lines are prone to geno...

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Detalles Bibliográficos
Autores principales: Jiang, Zhiwu, Wu, Di, Ye, Wei, Weng, Jianyu, Lai, Peilong, Shi, Pengcheng, Guo, Xutao, Huang, Guohua, Deng, Qiuhua, Tang, Yanlai, Zhao, Hongyu, Cui, Shuzhong, Lin, Simiao, Wang, Suna, Li, Baiheng, Wu, Qiting, Li, Yangqiu, Liu, Pentao, Pei, Duanqing, Du, Xin, Yao, Yao, Li, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739741/
https://www.ncbi.nlm.nih.gov/pubmed/29290956
http://dx.doi.org/10.18632/oncotarget.22466
Descripción
Sumario:Functional screening for compounds represents a major hurdle in the development of rational therapeutics for B-acute lymphoblastic leukemia (B-ALL). In addition, using cell lines as valid models for evaluating responses to novel drug therapies raises serious concerns, as cell lines are prone to genotypic/phenotypic drift and loss of heterogeneity in vitro. Here, we reported that OP9 cells, not OP9-derived adipocytes (OP9TA), support the growth of primary B-ALL cells in vitro. To identify the factors from OP9 cells that support the growth of primary B-ALL cells, we performed RNA-Seq to analyze the gene expression profiles of OP9 and OP9TA cells. We thus developed a defined, serum/feeder-free condition (FI76V) that can support the expansion of a range of clinically distinct primary B-ALL cells that still maintain their leukemia-initiating ability. We demonstrated the suitability of high-throughput drug screening based on our B-ALL cultured conditions. Upon screening 378 kinase inhibitors, we identified a cluster of 17 kinase inhibitors that can efficiently kill B-ALL cells in vitro. Importantly, we demonstrated the synergistic cytotoxicity of dinaciclib/BTG226 to B-ALL cells. Taken together, we developed a defined condition for the ex vivo expansion of primary B-ALL cells that is suitable for high-throughput screening of novel compounds.