Figure 5.

Microarray-based transcriptomic analysis of T-cell prolymphocytic leukemia (T-PLL) cells treated with LDC526. (A) Two examples of gene set enrichment analysis plots with potential functional relevance for the pharmacological effects of LDC526 in T-PLL cells. Genes found to be down-regulated in response to LDC526 were enriched for MYC targets and the IL6-JAK-STAT3- pathway. (B) Selected differentially regulated genes as indicated below the x axis. Bars represent the median; circles indicate results from individual patients/controls. (C) Down-regulation of MYC and MCL1 after incubation of T-PLL cells with LDC526 was validated at the protein level using western blot in four different patients. Left: MCL1 - patient samples comparing LDC526 with dimethyl sulfoxide (DMSO) in a concentration of 10 µM, right: MYC and MCL-1 sample T-PLL36 treated with different concentrations of LDC526. (D) Down-regulation of MYC mRNA levels after incubation of T-PLL cells with LDC526 is confirmed by quantitative reverse transcription polymerase chain reaction. (E) Genes down-regulated by LDC526 exhibit higher RNA decay rates as compared with genes with stable transcript levels.