SY-1425 shows similar response in RARA-high AML cell lines to APL

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SY-1425 shows similar response in RARA-high AML cell lines to APL SY-1425 shows similar response in RARA-high AML cell lines to APL. A, Gene expression response to SY-1425 (log2 fold change) by Affymetrix probes in the APL cell line NB-4 and the RARA-high cell lines OCI-AML3 and MV4-11. SY-1425 shows similar response in RARA-high AML cell lines to APL. A, Gene expression response to SY-1425 (log2 fold change) by Affymetrix probes in the APL cell line NB-4 and the RARA-high cell lines OCI-AML3 and MV4-11. Probes with FDR < 0.01 in joint group of OCI-AML3 and MV4-11 (n = 575) are shown. Probes are sorted by log2 fold change in the joint group of OCI-AML3 and MV4-11. B, Gene sets from the perturbation gene sets (MSigDB C2.CGP) that are enriched by GSEA in SY-1425 response in the RARA-high cell lines (top 5 gene sets by FDR, all of which are FDR < 0.01). Gene sets referencing tretinoin (ATRA) or APL are indicated in blue. X-axis indicates normalized enrichment score (NES). C, Log2 fold change of genes in RARA-high AML cell lines (OCI-AML3 and MV4-11) upon SY-1425. The 69 genes differentially expressed in both the RARA-high AML cell lines upon SY-1425 and the ex vivo APL patient samples upon retinoic acid treatment (Meani et al., ref. 42) are shown. Colors indicate the direction of change in the APL patient samples. D, Gene expression fold induction of TGM2 by SY-1425 (AML cell lines) or SY-1425 and ATRA (NB-4). Gray bars indicate RARA-low lines, red bars indicate RARA-high lines, and blue bars indicate the APL cell line. E, H3K27ac and RARα ChIP-seq signal at the TGM2 locus (chr20:36,749,636–36,841,254) in OCI-AML3 (RARA-high AML) and NB-4 (APL). Arrows indicate RARα binding site. F, GREAT analysis of gene sets enriched in H3K27ac peaks that are upregulated by SY-1425 in the RARA-high cell lines (OCI-AML3 and MV4-11). Top 5 (by FDR) perturbation gene sets are shown (full data in Supplementary Table S7). Michael R. McKeown et al. Cancer Discov 2017;7:1136-1153 ©2017 by American Association for Cancer Research