Division of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
Division of Pediatric Hematology-Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China.
Cell Biol Int. 2018 Sep;42(9):1228-1239. doi: 10.1002/cbin.10994. Epub 2018 Jun 15.
The survival rate of childhood acute lymphoblastic leukemia (ALL) has increased while that of Philadelphia-positive (Ph+) ALL remains low. CD19 is a B-cell specific molecule related to the survival and proliferation of normal B cells. However, there is little information available on the effects of CD19 on the biological behavior of Ph+ ALL cells. In this study, we explored a lentiviral vector-mediated short hairpin RNA (shRNA) expression vector to stably reduce CD19 expression in Ph+ ALL cell line SUP-B15 cells and investigated the effects of CD19 downregulation on cell proliferation, apoptosis, drug sensitivity, cell adhesion, cell migration and cell invasion in vitro. CD19 mRNA and protein expression levels were inhibited significantly by CD19 shRNA. Down-regulation of CD19 could inhibit cell proliferation, adhesion, migration and invasion, and increase cell apoptosis and the efficacy of chemotherapeutic agents and imatinib in SUP-B15 cells. Moreover, we found that down-regulation of CD19 expression inhibits cell proliferation and induces apoptosis in SUP-B15 cells in a p53-dependent manner. Taken together, our results suggest that lentiviral vector-mediated RNA interference of CD19 gene may be a promising strategy in the treatment of Ph+ ALL.
儿童急性淋巴细胞白血病 (ALL) 的存活率有所提高，而费城阳性 (Ph+) ALL 的存活率仍然较低。CD19 是一种与正常 B 细胞的存活和增殖有关的 B 细胞特异性分子。然而，关于 CD19 对 Ph+ALL 细胞生物学行为的影响的信息很少。在本研究中，我们探索了一种慢病毒载体介导的短发夹 RNA (shRNA) 表达载体，以稳定降低 Ph+ALL 细胞系 SUP-B15 细胞中的 CD19 表达，并研究了 CD19 下调对体外细胞增殖、凋亡、药物敏感性、细胞黏附、细胞迁移和细胞侵袭的影响。CD19 shRNA 显著抑制 CD19 mRNA 和蛋白表达。下调 CD19 可抑制 SUP-B15 细胞的增殖、黏附、迁移和侵袭，并增加细胞凋亡和化疗药物及伊马替尼的疗效。此外，我们发现下调 CD19 表达可抑制 SUP-B15 细胞的增殖并诱导其凋亡，这依赖于 p53。综上所述，我们的结果表明，慢病毒载体介导的 CD19 基因 RNA 干扰可能是治疗 Ph+ALL 的一种有前途的策略。
