Fig. 3: High-IL6/R pAML BM samples are highly distinct in terms of their immunological, transcriptional, and genomic characteristics. | Nature Communications

Fig. 3: High-IL6/R pAML BM samples are highly distinct in terms of their immunological, transcriptional, and genomic characteristics.

From: Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes

Fig. 3: High-IL6/R pAML BM samples are highly distinct in terms of their immunological, transcriptional, and genomic characteristics.

a In a UMAP projection using 1,506 immune genes, 287 high-IL6/R pAML, 306 low-IL6/R pAML and 45 NBM samples form distinct clusters, indicating broad immune differences. b Unsupervised hierarchical clustering of the expression levels (log2(TPM + 1)) of 82 immune and cancer genes divides high- and low-IL6/R samples (n = 287 and 306 respectively) into 3 groups with sharply distinct rates of MLL gene fusions, response to therapy (5-year EFS), and age at diagnosis. The minimum log2 expression value is zero and the maximum is 11.08. The minimum age is 18 days and the maximum is 26.85 years. The minimum EFS is 1 day, and the maximum is 8.2 years. c Oncoprint summarizing the distribution of somatic DNA alterations in 181 high-IL6/R pAML diagnostic samples from Cluster1 in (b). Each column represents one pAML BM sample. Each row indicates the occurrence of a genomic alteration with a colored cell. Chromosomal translocations are indicated in the “Fusions” row. The fusion partners of MLL translocations are indicated above the “Fusions” row. The color key at the bottom shows the colors used to indicate the types of gene-gene fusion displayed in the “Fusions” row (Inv16 = chromosome 16 inversion). The other 3 rows in the Oncoprint indicate the presence of RAS and FLT3 point mutations (PM) and FLT3 Internal Tandem Duplications (ITD). FLT3 point mutations that have been experimentally found to activate FLT3 signaling are shown in lighter red. The horizontal bars at the top indicate the grouping of high-IL6/R pAML samples into 5 highly recurrent genomic subgroups. Group1: MLL-rearrangements with co-occurring RAS or FLT3 point mutations. Group 2: samples with MLL-rearrangements only. Group 3: samples with diverse gene fusions and co-occurring RAS or FLT3 point mutations. Group 4: samples with RAS/FLT3 point mutations but no recurrent translocations. Group 5: samples with no detected recurrent genomic alterations.

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