American Society of Hematology

Figure 3.

Transcriptome-based mapping and aberrant erythroid regulators in AEL. (A) PCA of data from Differentiation Map (DMAP)33 with regression to cell types in an erythroid and myeloid compartment. The regression line fits to erythroid (green) and myeloid (gray) cells in the PCA space of genes significantly (FDR > 0.05, LogFC > 2) segregating each hematopoietic population: basophiles (BASO), common myeloid progenitor cells (CMP), eosinophil (EOS), erythrocytes (ERY), granulocyte-monocyte progenitor cells (GMP), granulocytes (GRAN), hematopoietic stem cells (HSC), megakaryocytes (MEGA), megakaryocytes-erythroid progenitor cells (MEP), and monocytes (MONO). (B) PCA with regression lines from plot (A) with projection of AEL patient samples. (C) PCA with regression lines from plot (A) with projection of AEL patient samples from our cohort (AEL cohort 1), from Iacobucci et al36 (AEL cohort 2) and MDS samples.39,40 (D) PCA with regression lines from plot (A) with projection of our AEL patient samples, AML and APL samples from the Blueprint consortium database. (E) PCA with regression lines from plot (A) with projection of AEL patient samples colored with KLF1, GATA1, and CEBPA expression and predicted activity. (F) Histogram representation of ERG, GFI1, RUNX1T1, ETO2, GATA3, and SKI gene expression in AEL patients. Positive patient samples (red bars) were defined as presenting an expression above the threshold set as fourfold the average of AEL samples. Dotted bars represent the average expression of AEL samples. (G) Table indicate patient samples presenting with genetic alteration (orange) or transcriptional alteration (blue) of GATA1-associated genes67-70 in 3 molecular subgroups of AEL: TP53-mutated, epigenetics, and others. (H) Kaplan-Meier survival plot of AEL patients grouped according to the presence (or absence) of genetic or transcriptional alterations defined in panel G. P value using log-rank Mantel-Cox test is indicated. (I) Kaplan-Meier survival plot of AEL patients from Iacobucci et al36 and grouped according to the presence (or not) of genetic or transcriptional alterations defined in panel G. P value using log-rank Mantel-Cox test is indicated.

Transcriptome-based mapping and aberrant erythroid regulators in AEL. (A) PCA of data from Differentiation Map (DMAP)³³ with regression to cell types in an erythroid and myeloid compartment. The regression line fits to erythroid (green) and myeloid (gray) cells in the PCA space of genes significantly (FDR > 0.05, LogFC > 2) segregating each hematopoietic population: basophiles (BASO), common myeloid progenitor cells (CMP), eosinophil (EOS), erythrocytes (ERY), granulocyte-monocyte progenitor cells (GMP), granulocytes (GRAN), hematopoietic stem cells (HSC), megakaryocytes (MEGA), megakaryocytes-erythroid progenitor cells (MEP), and monocytes (MONO). (B) PCA with regression lines from plot (A) with projection of AEL patient samples. (C) PCA with regression lines from plot (A) with projection of AEL patient samples from our cohort (AEL cohort 1), from Iacobucci et al³⁶ (AEL cohort 2) and MDS samples.^39,40 (D) PCA with regression lines from plot (A) with projection of our AEL patient samples, AML and APL samples from the Blueprint consortium database. (E) PCA with regression lines from plot (A) with projection of AEL patient samples colored with KLF1, GATA1, and CEBPA expression and predicted activity. (F) Histogram representation of ERG, GFI1, RUNX1T1, ETO2, GATA3, and SKI gene expression in AEL patients. Positive patient samples (red bars) were defined as presenting an expression above the threshold set as fourfold the average of AEL samples. Dotted bars represent the average expression of AEL samples. (G) Table indicate patient samples presenting with genetic alteration (orange) or transcriptional alteration (blue) of GATA1-associated genes^67-70 in 3 molecular subgroups of AEL: TP53-mutated, epigenetics, and others. (H) Kaplan-Meier survival plot of AEL patients grouped according to the presence (or absence) of genetic or transcriptional alterations defined in panel G. P value using log-rank Mantel-Cox test is indicated. (I) Kaplan-Meier survival plot of AEL patients from Iacobucci et al³⁶ and grouped according to the presence (or not) of genetic or transcriptional alterations defined in panel G. P value using log-rank Mantel-Cox test is indicated.

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