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PXD053611

PXD053611 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting Senescent Stem-Like Subpopulations in Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia
DescriptionPhiladelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype suggest incomplete oncogene addiction and partial response to tyrosine kinase inhibitor (TKI)-based therapies, highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, although the ABL-class Ph-like ALL subtype may be preferentially TKI-sensitive. Using bulk and single-cell multiomics analyses, we profiled residual cells from Ph-like ALL xenograft models treated in vivo with inhibitors to identify mechanisms of potential therapeutic escape. We identified a specific MYC dependency in Ph-like ALL and defined a leukemia cell subpopulation with senescence-associated stem cell-like features regulated by AP-1 transcription factors. This dormant ALL subpopulation could be eradicated by dual pharmacologic inhibition of JAK/STAT and BCL-2, providing mechanistic rationale for alternative therapeutic approaches.
HostingRepositoryPRIDE
AnnounceDate2025-01-28
AnnouncementXMLSubmission_2025-01-28_15:30:34.266.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDonggeun Lee
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-03 11:20:46ID requested
12025-01-28 15:30:34announced
Publication List
10.1182/BLOOD.2024026482;
Keyword List
submitter keyword: Ph-like ALL, senescence-associated stemness, MYC, tyrosine kinase inhibition, single-cell analysis, systems biology,AP-1
Contact List
Junmin Peng
contact affiliationSt. Jude Children's Research Hospital
contact emailjunmin.peng@stjude.org
lab head
Donggeun Lee
contact affiliationSt.Jude Children's Research Hospital
contact emaildonggeun.lee@stjude.org
dataset submitter
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Dataset FTP location
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