PXD026322-1

PXD026322 is an original dataset announced via ProteomeXchange.

Title	Activated interleukin-7 receptor signaling drives B-cell acute lymphoblastic leukemia in mice
Description	Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-ALL often associated with genetic variants that alter cytokine receptor signaling, including mutations in the interleukin-7 receptor (IL7R). To investigate whether IL7R variants are leukemia-initiating, we built mouse models expressing activated Il7r (aIL7R). B-cell intrinsic aIL7R mice developed spontaneous B-ALL, demonstrating sufficiency of Il7r activating mutations in leukemogenesis. Concomitant introduction of a knock-out allele in the associated adapter protein Lnk (encoded by Sh2b3) or a dominant-negative variant of the transcription factor Ikaros (Ikzf1) increased disease penetrance. The resulting murine leukemias displayed monoclonality and recurrent somatic Kras mutations and efficiently engrafted into immunocompetent mice. Phosphoproteomic analyses of aIL7R leukemic cells revealed constitutive Stat5 signaling and B cell receptor (BCR)-like signaling despite absence of surface pre-BCR. Finally, in vitro treatment of aIL7R leukemic B-cells with Jak, mTOR, or Syk inhibitors blocked growth, confirming that each pathway is active in this mouse model of IL7R-driven B-ALL.
HostingRepository	PRIDE
AnnounceDate	2021-06-28
AnnouncementXML	Submission_2021-06-28_09:52:33.794.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nathan Camp
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-27 22:41:36	ID requested
⏵ 1	2021-06-28 09:52:34	announced

Dataset with its publication pending

submitter keyword: Human, LC-MSMS, phosphoproteomics, Leukemia, IL7, cancer

Richard James
contact affiliation	Center for Immunity and Immunotherapies, Seattle Children's Research Institute. Department of Pediatrics, University of Washington. Seattle, WA USA
contact email	rickerj@uw.edu
lab head
Nathan Camp
contact affiliation	Seattle Children's Research Institute
contact email	nathandcamp@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026322
     1. Label: PRIDE project
     2. Name: Activated interleukin-7 receptor signaling drives B-cell acute lymphoblastic leukemia in mice