Pluto Biosciences, Inc

GSE126375: PAX5 belongs to a functional transcription factor network commonly targeted in B-lineage leukemia (murine)

Bulk RNA sequencing

One of the most frequently mutated proteins in human B-lineage leukemia, mutated in about one third of all cases, is the transcription factor PAX5. While reduced function of PAX5 has a clear connection to human malignancy there is limited evidence of a direct impact on the development and function of B-cell progenitors. One possible explanation to this comes from the finding that PAX5 mutated B-ALL display complex karyotypes and additional mutations, indicating that PAX5 might be just one component of a larger transcription factor network targeted in B-ALL. To investigate the functional network associated with PAX5 we used BioID technology to identify associated proteins. This revealed 239 proteins out of which several could be found mutated in human B-ALL. Most prominently we identified IKZF1, commonly mutated, and RUNX1, involved in the formation of ETV6-AML1 fusion protein formation, among the interaction partners. ChIP-seq as well as PLAC-seq analysis supported the idea that these factors share regulatory elements in human B-ALL cells. Gene expression and mutation analysis of both mouse models and primary human leukemia suggested that these factors form a functional gene regulatory network targeted by multiple mutations in human B-ALL.; ; Keywords: Expression profiling by high throughput sequencing SOURCE: Mikael Sigvardsson ( - Sigvardsson Lund University

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