Homo sapiens Transcriptome or Gene expression

Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA) sensitive Acute Promyelocytic Leukemia (APL) cell line (NB4), we derived an RA-resistant clone (MR2) characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We previously reported that RA-resistance in MR2 is associated with an altered pattern of high-molecular weight complexes binding to PML/RARA. We furthered this observation by identifying 8 members of these complexes, one of which was Nucleophosmin (NPM), a nucleolar protein intimately linked with the development of leukemia. Examination of the expression profile of NPM reveals a strong up-regulation at the protein level in the MR2 versus the NB4, without a corresponding robust increase in mRNA. Our RNA-seq based transcriptome analysis of both cell lines confirmed minimal difference in NPM transcript levels, and showed no differences in promoter, terminator or exon usage that would account for the dramatic increase in NPM protein levels. We also called variants from our RNA-Seq data to identify genomic differences between our two cell lines. There are 3 variants in the NPM1 gene (one in the 5' UTR and two intronic) in the MR2 cell line, which might be involved in the enhanced translation of NPM.