PXD066096

PXD066096 is an original dataset announced via ProteomeXchange.

Title	PAMD-Ch17, a Polymeric Analog of Plerixafor, Induces Mitochondrial Dysfunction in T-ALL Cells Independent of CXCR4
Description	PAMD-Ch17 is a polymer composed of the CXCR4 inhibitor AMD3100/Plerixafor with a cholesterol modification. In previous work, we showed that PAMD-Ch17, but not AMD3100, induces cell death and differentiation in mouse Acute Myeloid Leukemia cells. To investigate the mechanism of PAMD-Ch17’s novel anti-leukemic effects, we tested PAMD-Ch17 against a panel of human leukemia cell lines and found that PAMD-Ch17 is effective against a variety of acute leukemias, with T-ALL cell lines being highly sensitive. Surprisingly, CXCR4 knock out T-ALL cells were equally sensitive to PAMD-Ch17. Using a fluorescently tagged PAMD-Ch17, we found that the drug colocalized to mitochondria. We also found that PAMD-Ch17 induced changes in expression of genes related to mitochondrial function, increased levels of mitochondrial superoxide, and decreased mitochondrial membrane potential. Using seahorse assays, we found that PAMD-Ch17 decreased baseline oxygen consumption, ATP production, and proton leakage. In addition, we identified ATP Synthase subunits as binding partners of PAMD-Ch17 and showed that the polymer, but not AMD3100, inhibited ATP Synthase activity. In mouse primary T-ALL but not healthy bone marrow cells, PAMD-Ch17 induced both mitochondrial superoxide and cell death. Using human bone marrow organoids, we found that PAMD-Ch17 induced mitochondrial superoxide and cell death in patient T-ALL cells, but not in healthy stromal and hematopoietic cells. Collectively, our results indicate that PAMD-Ch17 has anti-leukemic effects against T-ALL cells but not healthy cells, likely mediated through a CXCR4 independent, mitochondrial based mechanism. These findings support further development of PAMDs as potential therapeutics for patients with T-ALL.
HostingRepository	PRIDE
AnnounceDate	2026-02-16
AnnouncementXML	Submission_2026-02-16_13:28:52.425.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD066096
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	R. Katherine Hyde
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-13 14:08:32	ID requested
⏵ 1	2026-02-16 13:28:53	announced

10.6019/PXD066096;

Lam C, Dhir A, Jogdeo CM, Panda S, Kapoor E, Tang S, Rivero V, McIntyre EM, Coulter DW, Xiao P, Black AR, Hewitt K, Swenson SA, Romanova S, Oupicky D, Hyde RK, PAMD-Ch17, a Polymeric Analog of Plerixafor, Induces Mitochondrial Dysfunction in T-ALL Cells Independent of CXCR4. bioRxiv, ():(2025) [pubmed]

10.1101/2025.05.28.656643;

submitter keyword: polymeric drugs, AMD3100, CXCR4,Leukemia, T-ALL

R. Katherine Hyde
contact affiliation	Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha NE
contact email	kate.hyde@unmc.edu
lab head
R. Katherine Hyde
contact affiliation	University of Nebraska Medical Center
contact email	kate.hyde@unmc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD066096

PRIDE project URI

• PRIDE
  1. PXD066096
     1. Label: PRIDE project
     2. Name: PAMD-Ch17, a Polymeric Analog of Plerixafor, Induces Mitochondrial Dysfunction in T-ALL Cells Independent of CXCR4