MassIVE MSV000081327

Complete Public PXD007046

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/PI3K/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

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Description

Mutations in the interleukin-7 receptor (IL7R) or the JAK3 kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here, we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells and human JAK3 mutated T-ALL samples. Novel peptides shown to be downstream of mutant JAK3 regulating RNA metabolism as well as epigenetic and apoptotic processes were validated using targeted PRM proteomics. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: T-ALL ; JAK3 ; L857Q ; M511I ; TMT10plex ; DDA ; PRM ; Phosphoproteomic Profiling

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Principal Investigators:
(in alphabetical order) 		Dr. Matt Dun, University of Newcastle, Australia
Submitting User: Matt_MOG17

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