Bulk RNA sequencing analysis of Lin- leukemia BCR-ABL and BCR-ABL/MSI2-HOXA9 cells (post-transplantation)

To understand how the MSI2-HOXA9 translocation triggers
blast crisis CML (bcCML), we compared gene expression patterns in BCR-ABL
and BCR-ABL/MSI2-HOXA9-driven disease. RNA-seq analysis
was carried out on lineage
negative cells from leukemia established
with BCR-ABL alone or with a combination of  BCR-ABL and
MSI2-HOXA9. Network mapping of all differentially expressed genes
(q-value <0.05) using non-redundant functional
grouping revealed an enrichment of metabolic processes with
oncogenic pathways and developmental programs. Programs that
were dominantly
upregulated by MSI2/HOXA9 were those involved
in development, including Aldh1a1, Erbb3, and Kit, consistent
with BCR-ABL/MSI2-HOXA9 driving a more undifferentiated disease, known
oncogenes, including Frat1, Map7, and Fzd3, and components of the
mitochondria including mt-Co2, mt-Atp8, and
mt-Nd5. Among the genes most
enriched in BCR-ABL/MSI2-HOXA9-driven bcCML were key components of the mitochondrial respiratory chain, including Complex I, Complex III, Complex IV, and the F0 subunit of ATP synthase (mt-Atp6 and mt-Atp8).