Supplementary Fig. 1: Molecularly and clinically distinct subtypes of AML based on global and IRAK4 RNA isoform expression.

(a) Overview of RNA isoform switching analysis in AML with the corresponding figures and panels shown in parentheses. (b) Schematic representation of expression-level regulation versus isoform-level regulation of RNA isoforms in hypothetical samples. (c) Overall survival analysis of the 3 major groupings of AML (Group 1, blue; Group 2, red; Group 3, green) characterized by distinct patterns of differential isoform usage identified in Fig. 1b. Likelihood ratio test, Multivariate P = 0.06. (d) Exon usage of innate immune genes undergoing isoform switching in AML (Group 2) was correlated to overall survival of AML. Shown is the z-score correlation of IRAK4 exon usage to overall survival of AML patients. In red, exon 4 significantly correlates with worse overall survival of AML patients. (e) Relative expression of IRAK4-L to IRAK4-S in normal tissue (blue) relative to cancer tissue (red) for the indicated cancers analyzed in TCGA. Breast cancer (n = 1093); normal tissue (n = 112). Colon cancer (n = 285); normal tissue (n = 41). Lung cancer (n = 515); normal tissue (n = 59). The P value is indicated for each pair of samples and was determined by Welch’s t-test. (f) Sequence analysis of the IRAK4 exon 4 cassette using primers flanking exon junctions 3-4, 4-5, and 3–5 isolated from THP1 cells.