Figure 5
Figure 5. Abrogation of lincRNA-3q activity by BET inhibition in BPDCN and AML leukemia cells. (A) Tumor growth kinetics measured in nude mice engrafted with shCtrl or shlincRNA-3q-transduced CAL-1 cells (left); bioluminescence imaging for 2 representative mice (day 14) (middle); and quantification of tumor bioluminescence (7 and 14 days postinjection) for each group (right). *P < .05, **P < .01 by Student t test; n = 8 for each group. (B) Genomic organization of the lincRNA-3q locus and BRD4 ChIP-sequencing analysis (ArrayExpress accession number ERP004614) showing promoter occupancy by BRD4 in MUTZ-3 cell line (3q rearrranged AML) compared with K562 cell line (no 3q rearrangement). ENCODE data showing positions of active chromatin marks and phospho-RNA polymerase II (Pol II) binding, as indicated. (C) Anti-BRD4 and anti-AcH3 ChIP at the promoter region of lincRNA-3q in CAL-1 and U937 cells, as indicated. (D) RT-qPCR-derived lincRNA-3q expression in MUTZ3, K562, U937, and CAL-1 cells treated with 1 μM JQ1 at the time indicated. *P < .05, **P < .01 by Wilcoxon test; n = 3. (E) Venn diagrams (left) and heatmap (right) showing time course of differential gene expression of lincRNA-3q targets upon JQ1 treatment in CAL-1, as indicated. (F) Tumor growth kinetics measured in nude mice bearing tumors derived from CAL-1 cell lines after control or JQ1 treatment (left); bioluminescence imaging for 2 representative mice (day 14) (middle); and quantification of tumor bioluminescence (7 and 14 days posttreatment) for each group (right). *P < .05, **P < .01 by Student t test; n = 6 for each group. AcH3, acetylated histone H3; BET, bromodomain and extraterminal domain; Ig, immunoglobulin; LP, lincRNA ChIP Primer.

Abrogation of lincRNA-3q activity by BET inhibition in BPDCN and AML leukemia cells. (A) Tumor growth kinetics measured in nude mice engrafted with shCtrl or shlincRNA-3q-transduced CAL-1 cells (left); bioluminescence imaging for 2 representative mice (day 14) (middle); and quantification of tumor bioluminescence (7 and 14 days postinjection) for each group (right). *P < .05, **P < .01 by Student t test; n = 8 for each group. (B) Genomic organization of the lincRNA-3q locus and BRD4 ChIP-sequencing analysis (ArrayExpress accession number ERP004614) showing promoter occupancy by BRD4 in MUTZ-3 cell line (3q rearrranged AML) compared with K562 cell line (no 3q rearrangement). ENCODE data showing positions of active chromatin marks and phospho-RNA polymerase II (Pol II) binding, as indicated. (C) Anti-BRD4 and anti-AcH3 ChIP at the promoter region of lincRNA-3q in CAL-1 and U937 cells, as indicated. (D) RT-qPCR-derived lincRNA-3q expression in MUTZ3, K562, U937, and CAL-1 cells treated with 1 μM JQ1 at the time indicated. *P < .05, **P < .01 by Wilcoxon test; n = 3. (E) Venn diagrams (left) and heatmap (right) showing time course of differential gene expression of lincRNA-3q targets upon JQ1 treatment in CAL-1, as indicated. (F) Tumor growth kinetics measured in nude mice bearing tumors derived from CAL-1 cell lines after control or JQ1 treatment (left); bioluminescence imaging for 2 representative mice (day 14) (middle); and quantification of tumor bioluminescence (7 and 14 days posttreatment) for each group (right). *P < .05, **P < .01 by Student t test; n = 6 for each group. AcH3, acetylated histone H3; BET, bromodomain and extraterminal domain; Ig, immunoglobulin; LP, lincRNA ChIP Primer.

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