STAT5 is insufficient to drive steroid resistance in T-cell acute lymphoblastic leukemia despite activation of BCL2 and BCLXL upon glucocorticoid treatment

Overexpression of STAT5B_N642H mutant results in the ligand-independent activation of STAT5 signaling and STAT5 transcriptional activity, without affecting MAPK-ERK or PI3K-AKT signalling pathways. Overexpression of wild type (WT) STAT5B did not activate STAT5 signaling . Treatment with prednisolone boosts the expression of STAT5_N642H regulated genes, whereas NR3C1 can bind at gene loci of STAT5 regulated genes. Despite the steroid-enhanced upregulation of anti-apoptotic targets, the mutant cell line remaind sensitive to steroid treatment. We studied potential co-regulation and co-binding of NR3C1 and STAT5B in STAT5B_N642H and STAT5B_WT overexpressing cells, treated and untreated with prednisolone. Overall design: NR3C1 and STAT5B binding for SUPT-1 cells overexpressing STAT5 wild type (WT) or STAT5 mutant (N642H), in the absence or presence of prednisolone treatment

STAT5B_N642H突变体的过表达可引发STAT5信号通路的配体非依赖性激活，并提升STAT5的转录活性，且不会影响MAPK-ERK或PI3K-AKT信号通路。野生型（WT）STAT5B的过表达无法激活STAT5信号通路。泼尼松龙（prednisolone）处理可增强STAT5_N642H调控基因的表达，而NR3C1能够结合在STAT5调控基因的基因座区域。尽管类固醇激素可增强抗凋亡靶基因的上调表达，该突变体细胞系仍对类固醇处理敏感。我们研究了经泼尼松龙处理与未处理的、分别过表达STAT5B_N642H和STAT5B_WT的细胞中，NR3C1与STAT5B的潜在共调控及共结合情况。整体实验设计：针对过表达野生型（WT）STAT5或STAT5突变体（N642H）的SUPT-1细胞，在有无泼尼松龙处理的条件下，检测NR3C1与STAT5B的结合情况。