American Society of Hematology

Figure 4

$Figure 4. Degree of stemness of the AML transcriptome is related to activity of the ERG +85 stem cell enhancer. (A) ChIP-chip profiles for active (H3K9/14Ac) and inactive (H3K27Me3) histone marks across the ERG locus are shown for normal CD34+ stem/progenitors, mature neutrophils, and CD3+ T cells. CD34+ cells show active marks at both promoters and the +85 enhancer and no inactive marks. Neutrophils show bivalency at the distal promoter and active marks at the proximal promoter and enhancer. T cells show no active marks and modest enrichment of inactive marks at these sites. (B) Abundance and types of ERG transcripts in each cell type shown in the previous panel. (C) A 3-dimensional display of normal CD34+ stem/progenitors and 26 AML samples plotted according to normalized levels of enrichment of specific histone marks at their ERG promoter/enhancer elements. Individual AML samples were clustered as before into 4 groups, with the arithmetic mean of each group plotted in the figure. Samples in the red and yellow groups in particular display more epigenetic similarity with normal CD34+ stem/progenitors compared with samples in the green group. (D) A PCA of global gene expression profiles of normal CD34+ stem/progenitors and 25 AML samples is shown. As before, the arithmetic mean of each group is plotted. The transcriptomes of AML samples in the red group that, along with the yellow group, shares the closest epigenetic identity (at the ERG locus) to normal CD34+ stem/progenitors also display the closest transcriptional identity. There is progressive loss of transcriptional similarity to CD34+ cells as the AMLs lose their epigenetic identity (at the ERG locus) with CD34+ cells. (E) A PCA of transcriptomes of NOD/SCID engrafting and nonengrafting AML fractions3 computed with the transcriptomes of our 25 AML samples is shown. As before, the arithmetic mean of each group is plotted. The AML samples that lack an active enhancer mark (green group) cluster closer to the nonengrafting AML fraction, whereas those samples with an active enhancer and transcriptome that is closer to normal CD34+ cells (red and yellow) cluster closer to engrafting AML fractions.$

Degree of stemness of the AML transcriptome is related to activity of the ERG +85 stem cell enhancer. (A) ChIP-chip profiles for active (H3K9/14Ac) and inactive (H3K27Me3) histone marks across the ERG locus are shown for normal CD34⁺ stem/progenitors, mature neutrophils, and CD3⁺ T cells. CD34⁺ cells show active marks at both promoters and the +85 enhancer and no inactive marks. Neutrophils show bivalency at the distal promoter and active marks at the proximal promoter and enhancer. T cells show no active marks and modest enrichment of inactive marks at these sites. (B) Abundance and types of ERG transcripts in each cell type shown in the previous panel. (C) A 3-dimensional display of normal CD34⁺ stem/progenitors and 26 AML samples plotted according to normalized levels of enrichment of specific histone marks at their ERG promoter/enhancer elements. Individual AML samples were clustered as before into 4 groups, with the arithmetic mean of each group plotted in the figure. Samples in the red and yellow groups in particular display more epigenetic similarity with normal CD34⁺ stem/progenitors compared with samples in the green group. (D) A PCA of global gene expression profiles of normal CD34⁺ stem/progenitors and 25 AML samples is shown. As before, the arithmetic mean of each group is plotted. The transcriptomes of AML samples in the red group that, along with the yellow group, shares the closest epigenetic identity (at the ERG locus) to normal CD34⁺ stem/progenitors also display the closest transcriptional identity. There is progressive loss of transcriptional similarity to CD34⁺ cells as the AMLs lose their epigenetic identity (at the ERG locus) with CD34⁺ cells. (E) A PCA of transcriptomes of NOD/SCID engrafting and nonengrafting AML fractions³ computed with the transcriptomes of our 25 AML samples is shown. As before, the arithmetic mean of each group is plotted. The AML samples that lack an active enhancer mark (green group) cluster closer to the nonengrafting AML fraction, whereas those samples with an active enhancer and transcriptome that is closer to normal CD34⁺ cells (red and yellow) cluster closer to engrafting AML fractions.

This Feature Is Available To Subscribers Only