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Figure 5. High MIXL1 expression denotes a distinct subset of AML(A) Mutually exclusive expression of MIXL1 and HOXA9 in distinct FAB subsets. The RNA-seq data are publicly available from the TCGA website (https://tcga-data.nci.nih.gov/tcga/). 177 samples of Acute Myeloid Leukemia classified by leukemia French American British morphology code (FAB) and a total of 20319 genes with expression values in the RPKM format were included. The data were quantile normalized using the normalize Quantiles function from the limma package. The expression levels of MIXL1 and HOXA9 of the 177 samples from 8 FAB categories were plotted in the heatmap using the heatmap.2 function in the gplots package of R 3.1.1. Within each FAB category, the samples were ordered according to the expression value of the MIXL1 gene. (B) MIXL1 upregulation identifies a non-overlapping AML subset from those expressing CDX2, HOXA9, or HLX. TCGA AML patient dataset was queried for alterations in expression as determined by RNA-Seq across 166 AML cases through the cBioPortal database. Each column represents a case of AML. MIXL1 is amplified or upregulated in 13% of the total AML cases. Note the predominantly non-overlapping expression patterns of MIXL1, CDX2, HOXA9, and HLX. (C) Seventy-six percent (16/21) of MIXL1-expressing cases in TCGA AML dataset harbored somatic mutations common in AML (NPM1, FLT3, DNMT3A, IDH1, RUNX1 JAK3, and TP53). Each column represents a case. (D) Relapse-free survival of MIXL1-expressing cases is lower than that of non–MIXL1-expressing cases. TCGA AML cases were separated into two groups: MIXL1-expressing (increase in expression or amplified) and non–MIXL1-expressing. Relapse-free survival was then compared between the two groups using the Kaplan-Meier method.

Image published in: Raymond A et al. (2014)

Copyright: © 2014 Raymond et al. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license

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