A B-cell acute lymphoblastic leukemia regulatory network defines novel therapeutic targets in IGH-CRLF2 patients
Sana Badri, Beth Carella, Priscillia Lhoumaud, Dayanne M. Castro, Ramya Raviram, Aaron Watters, Richard Bonneau, Jane A. Skok
Received Date: 28th May 19
CRLF2 overexpression in B-ALL patients with an IGH-CRLF2 translocation activates JAK-STAT, PI3K and ERK/MAPK signaling pathways. Although inhibitors of these pathways are available, investigating alternate targets could reduce treatment-associated toxicities. Comparing RNA-seq from IGH-CRLF2 and non-translocated patients we defined a translocation gene signature. Next, we assembled a B-ALL cancer-specific regulatory network using 529 B-ALL patient samples from the NCI TARGET database coupled with priors generated from ATAC-seq peak TF-motif analysis. The network was used to infer differential changes in TF activities predicted to control IGH-CRLF2 deregulated genes, thereby enabling identification of translocation-associated pathways and potential new therapeutic targets.
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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.