American Society of Hematology

Figure 1

$Figure 1. CEBPA silencing and promoter hypermethylation are associated with AMLs sharing a CEBPA mutant gene expression signature in GEP cluster no. 4. (A) Pairwise correlations between gene expression profiles of 285 AML samples calculated on the basis of 2856 probe sets are displayed as described.4 Colors of boxes visualize Pearson correlation coefficient: deeper red indicates higher positive correlation; deeper blue indicates higher negative correlation. Sixteen distinct clusters were previously distinguished, which can be recognized by the red blocks showing high correlation along the diagonal.4 Cluster no. 4 and cluster no. 15, associated with CEBPA mutations, are enlarged. The bar and histogram next to each patient represent CEBPA mutation status and CEBPA expression level, respectively. CEBPA mutation status: presence (“mut,” red) or absence (“wt,” green) of mutations in bZIP region and/or N-terminus. These data indicate that in leukemias in cluster no. 4 lacking mutations, CEBPA expression is low or absent. In cluster no. 4, the order of samples, from top to bottom, is as follows: no. 3327, no. 2242 (both CEBPA mutant); no. 2668, no. 2238, no. 3314, no. 2686, no. 3483, no. 3491 (all 6 without CEBPA mutation); no. 2218, no. 1316, no. 2273, no. 2545, no. 2169, no. 2753, and no. 2192 (all 7 CEBPA mutant). (B, upper part) Schematic representation of the chromosomal region surrounding the transcriptional start of the CEBPA gene. Numbers indicate position relative to CEBPA transcriptional start. Vertical lines represent CpG dinucleotides; “transcription” indicates transcriptional start; “ATG,” translational start site. (Lower part) Level of cytosine methylation in the region surrounding the CEBPA transcriptional start site of the 6 AML cases in cluster no. 4 with low CEBPA expression, with patient numbers on the left. Every cytosine in a CpG dinucleotide is depicted as a circle. For each of these cytosines, the fraction of methylated residues was determined, which is visualized by the color of the circle: methylated (> 75% of all cytosines methylated, black), partly methylated (25%-75% methylated, gray), unmethylated (< 25% methylated, white).$

CEBPA silencing and promoter hypermethylation are associated with AMLs sharing a CEBPA mutant gene expression signature in GEP cluster no. 4. (A) Pairwise correlations between gene expression profiles of 285 AML samples calculated on the basis of 2856 probe sets are displayed as described.⁴ Colors of boxes visualize Pearson correlation coefficient: deeper red indicates higher positive correlation; deeper blue indicates higher negative correlation. Sixteen distinct clusters were previously distinguished, which can be recognized by the red blocks showing high correlation along the diagonal.⁴ Cluster no. 4 and cluster no. 15, associated with CEBPA mutations, are enlarged. The bar and histogram next to each patient represent CEBPA mutation status and CEBPA expression level, respectively. CEBPA mutation status: presence (“mut,” red) or absence (“wt,” green) of mutations in bZIP region and/or N-terminus. These data indicate that in leukemias in cluster no. 4 lacking mutations, CEBPA expression is low or absent. In cluster no. 4, the order of samples, from top to bottom, is as follows: no. 3327, no. 2242 (both CEBPA mutant); no. 2668, no. 2238, no. 3314, no. 2686, no. 3483, no. 3491 (all 6 without CEBPA mutation); no. 2218, no. 1316, no. 2273, no. 2545, no. 2169, no. 2753, and no. 2192 (all 7 CEBPA mutant). (B, upper part) Schematic representation of the chromosomal region surrounding the transcriptional start of the CEBPA gene. Numbers indicate position relative to CEBPA transcriptional start. Vertical lines represent CpG dinucleotides; “transcription” indicates transcriptional start; “ATG,” translational start site. (Lower part) Level of cytosine methylation in the region surrounding the CEBPA transcriptional start site of the 6 AML cases in cluster no. 4 with low CEBPA expression, with patient numbers on the left. Every cytosine in a CpG dinucleotide is depicted as a circle. For each of these cytosines, the fraction of methylated residues was determined, which is visualized by the color of the circle: methylated (> 75% of all cytosines methylated, black), partly methylated (25%-75% methylated, gray), unmethylated (< 25% methylated, white).

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