PXD053611

PXD053611 is an original dataset announced via ProteomeXchange.

Title	Targeting Senescent Stem-Like Subpopulations in Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia
Description	Philadelphia 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.
HostingRepository	PRIDE
AnnounceDate	2025-01-28
AnnouncementXML	Submission_2025-01-28_15:30:34.266.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Donggeun Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-03 11:20:46	ID requested
⏵ 1	2025-01-28 15:30:34	announced

10.1182/BLOOD.2024026482;

submitter keyword: Ph-like ALL, senescence-associated stemness, MYC, tyrosine kinase inhibition, single-cell analysis, systems biology,AP-1

Junmin Peng
contact affiliation	St. Jude Children's Research Hospital
contact email	junmin.peng@stjude.org
lab head
Donggeun Lee
contact affiliation	St.Jude Children's Research Hospital
contact email	donggeun.lee@stjude.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053611
     1. Label: PRIDE project
     2. Name: Targeting Senescent Stem-Like Subpopulations in Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia