Figure 3.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 regulates MYC signaling in B-cell acute lymphoblastic leukemia. (A) RNA gene expression analysis of 12 B-cell acute lymphoblastic leukemia (B-ALL) cell lines treated with 2 mM of MI-2 for 8 hours (h) was performed by RNA sequencing. The heatmap represents 1,036 whose expression changed ≥ 2-fold at FDR < 0.1 (275 down- and 761 up-regulated). Gene expression is median centered and scaled as indicated. Each column represents a sample, and each row represents a gene. Gene symbols highlight select genes. (B) An enrichment plot representing the inhibitory effect of MI-2 on the most affected MYC gene set as identified by gene set enrichment analysis. (C) Decrease in the signature score of the MYC gene set shown in (B) computed as the average of the mRNA expression level of the leading edge genes of MI-2–treated samples minus the corresponding control. The leading edge genes represent the genes of this MYC gene set most significantly differentially expressed in the experimental data, as determined by gene set enrichment analysis. (D) Immunoblot showing Myc expression changes in whole cell lysates following 0-2 mM MI-2 treatment for 8 h. (E) Quantification of FBXW7 isoforms changes (relative change/Actin) following treatment with 1 mM MI-2 for 1-8 h. FDR: false discovery rate; NES: normalized enrichment score; MALT1: mucosa-associated lymphoid tissue lymphoma translocation protein 1.