Investigating the AZDR1208 resistance in HSB-2 cells

The study uses RNA sequencing to profile AZD1208 resistant (AZDR) vs AZD1208 sensitive HSB-2 cells. PIM inhibitor treatment decreases leukemia burden in early T-cell precursor acute lymphoblastic leukemias (ETP-ALL) both in vitro and in vivo. However, prolonged treatment of ETP-ALL with PIM kinase inhibitors results in PIM inhibitor resistance. The analysis revealed that the HOXA9, mTOR, MYC, NF-B, and PI3K-AKT pathways were activated in PIM inhibitor resistant ETP-ALL PIM inhibitor resistance in HSB-2 cells was induced by growing the cells in the presence of increasing doses of AZD1208 over a 4 month period until resulting cell populations were able to maintain their growth at 1 µM AZD1208. RNA sequencing was utilized to define differentially expressed genes.

本研究采用RNA测序（RNA sequencing）对比分析AZD1208耐药（AZDR）与AZD1208敏感的HSB-2细胞的转录组特征。PIM抑制剂（PIM inhibitor）在体外与体内均可降低早期T细胞前体急性淋巴细胞白血病（ETP-ALL）的肿瘤负荷，但长期使用PIM激酶抑制剂（PIM kinase inhibitors）治疗ETP-ALL可诱导产生PIM抑制剂耐药性。分析结果显示，在PIM抑制剂耐药的ETP-ALL中，HOXA9、mTOR、MYC、NF-κB及PI3K-AKT通路被激活。本研究通过在为期4个月的培养过程中，以逐步递增剂量的AZD1208处理细胞，直至最终获得的细胞群可在1 μM AZD1208环境中维持生长，成功诱导得到HSB-2细胞的PIM抑制剂耐药表型。本研究利用RNA测序鉴定了差异表达基因。