Inhibition of BCL11B induces downregulation of PTK7 and results in growth retardation and apoptosis in T-cell acute lymphoblastic leukemia

• Main Authors: Kehan Li (Author), Cunte Chen (Author), Rili Gao (Author), Xibao Yu (Author), Youxue Huang (Author), Zheng Chen (Author), Zhuandi Liu (Author), Shaohua Chen (Author), Gengxin Luo (Author), Xin Huang (Author), Grzegorz K. Przybylski (Author), Yangqiu Li (Author), Chengwu Zeng (Author)
• Format: Book
• Published: BMC, 2021-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of leukemia with poor prognosis, and biomarkers and novel therapeutic targets are urgently needed for this disease. Our previous studies have found that inhibition of the B-cell leukemia/lymphoma 11B (BCL11B) gene could significantly promote the apoptosis and growth retardation of T-ALL cells, but the molecular mechanism underlying this effect remains unclear. This study intends to investigate genes downstream of BCL11B and further explore its function in T-ALL cells. We found that PTK7 was a potential downstream target of BCL11B in T-ALL. Compared with the healthy individuals (HIs), PTK7 was overexpressed in T-ALL cells, and BCL11B expression was positively correlated with PTK7 expression. Importantly, BCL11B knockdown reduced PTK7 expression in T-ALL cells. Similar to the effects of BCL11B silencing, downregulation of PTK7 inhibited cell proliferation and induced apoptosis in Molt-4 cells via up-regulating the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and p27. Altogether, our studies suggest that PTK7 is a potential downstream target of BCL11B, and downregulation of PTK7 expression via inhibition of the BCL11B pathway induces growth retardation and apoptosis in T-ALL cells.

Item Description

10.1186/s40364-021-00270-3
2050-7771