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. 2020 Dec 1;105(12):2864-2867.
doi: 10.3324/haematol.2019.240721.

Chronic lymphocytic leukemias with trisomy 12 show a distinct DNA methylation profile linked to altered chromatin activation

Maria Tsagiopoulou  1 , Vicente Chapaprieta  2 , Martí Duran-Ferrer  2 , Theodoros Moysiadis  1 , Fotis Psomopoulos  1 , Panagoula Kollia  3 , Nikos Papakonstantinou  1 , Elias Campo  2 , Kostas Stamatopoulos  1 , Jose I Martin-Subero  2
Affiliations

Chronic lymphocytic leukemias with trisomy 12 show a distinct DNA methylation profile linked to altered chromatin activation

Maria Tsagiopoulou et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
DNA methylation analysis of del(13q), del(11q) and +12 chronic lymphocytic leukemia. (A) Barplot showing the overall DNA methylation levels in the examined cytogenetic subgroups and normal B cells (+12 vs. del(11q), P=0.006; +12 vs. del(13q), P=7.166e-08; del(13q) vs. del(11q), P= 0.01). (B) Principal component analysis showing components 1 and 5 in the cytogenetic subgroups and normal B cells. (C) Number of differential methylation CpG (DMCpG) resulting from the comparison of each cytogenetic subgroup versus all the others chronic lymphocytic leukemia (CLL) cases. The white bar represents the IGHVunmutated CLL (U-CLL) while the grey bar represents the IGHV-mutated CLL (M-CLL) cases. (D) Hierarchical clustering based on 646 DMCpG of +12 U-CLL cases as compared to other U-CLL and normal B cells. (E) Enrichment analysis of DMCpG hypomethylated in +12 U-CLL on gene location, location related to islands and chromatin states of memory B cells. The density represents the log2FC of the enriched CpG compared to the background in each condition (hypo- and hypermethylation). Each color is linked to a particular subgroup: orange for del(11q), blue for del(13q), red for +12, green for memory B cells and yellow for naive B cells. PC: principal component, FC: fold change.
Figure 2.
Figure 2.
Characterization of the chromatin and transcriptional features of regions de novo hypomethylated in +12 cases. (A) DNA methylation levels of 312 CpG that overlap with H3K27ac-containing regions. (B) Heatmap of signal intensities of H3K27ac regions associated with CpG from panel (A). (C) Heatmap of the 35 hypomethylated regions showing significantly higher H3K27ac levels in IGHV-unmutated CLL (U-CLL) compared with cases without +12. (D) Scheme of the strategy used to detect accessible sites within regions with differential methylation CpG (DMCpG) and increased chromatin activity. (E) Transcription factors whose binding sites are significantly enriched in accessible regions within hypomethylated and active regulatory elements. (F) Heatmap showing the relative expression levels of the 25 genes epigenetically-upregulated in +12 U-CLL compared with cases lacking +12. (G) On the left, a genome browser display of the RUNX3 region including H3K27ac and gene expression of two representative +12 and non +12 U-CLL, as well as DNA methylation data from all U-CLL studied. The red square points to the distant regulatory region that becomes hypomethylated and active in +12 U-CLL. On the right, a zoom-in panel of the H3K27ac levels of the distant enhancer region as well as box plots of H3K27ac and gene expression in all U-CLL studied. Each color is linked to a particular subgroup: orange for del(11q), blue for del(13q), red for +12.
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References

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