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Figure 4 | Journal of Hematology & Oncology

Figure 4

From: YM155 potently kills acute lymphoblastic leukemia cells through activation of the DNA damage pathway

Figure 4

YM155 activates DNA damage response. (A) YM155 has multiple effects on RNA expression. REH (wild-type p53), SUPB15 (wild-type p53), and K562 (mutant p53) cells were treated with 100 nM YM155 or vehicle for 24 h and mRNA expression levels of 84 genes were evaluated using the P53 RT2 Array. Treatment with YM155 caused about a twofold decrease in survivin mRNA (BIRC5) in the p53 intact cells, but had minimal impact on survivin expression in K562 cells despite potent effects of YM155 on K562 cell growth/viability (IC50 of <10nM [13]). Meanwhile, other genes such as JUN and GADD45A involved in DNA damage response exhibit increased expression after YM155 treatment in all three cell lines. (B) YM155 treatment greatly enhances phosphorylation of Chk2. REH, SUPB15, and HAL01 cells were treated with either vehicle or 100 nM YM155 for 24 h, and protein phosphorylation patterns were assessed using Proteome Profiler Arrays. Values were quantified and normalized to untreated control for each site. REH cells show p53 and Chk2 with the largest change in phosphorylation. SUPB15 shows only Chk2 with the largest change in phosphorylation. HAL01 cells, known to be resistant to YM155 showed minimal change in phosphorylation.

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