PXD026296

PXD026296 is an original dataset announced via ProteomeXchange.

Title	Adverse stem cell features in a single AML sample predict clinical outcome in AML patient cohorts
Description	Patients with acute myeloid leukemia (AML) suffer dismal prognosis and the most adverse subpopulation within each tumor determines patient’s prognosis. To better understand challenging features in AML, we studied individual stem cells from a single AML sample, complementing genomic with in vivo functional studies. Primary tumor cells from an AML patient’s first and second relapse were transplanted into NSG mice to establish serially transplantable patient derived xenografts (PDX). In an innovative approach, twelve derivative PDX clones were generated thereof, each derived from a single AML stem cell as proven by molecular barcoding, and were color-marked to facilitate multiplex competitive in vivo assays. PDX clones consisted of four different genomic clusters; one cluster displayed resistance against Cytarabine treatment, while two other clusters harbored increased stem cell potential, indicating that stemness and treatment resistance had evolved independently in the sample. In vivo functional data correlated closely with the phylogenetic tree calculated from exome data. The Cytarabine-resistant cluster was characterized by a distinct gene expression profile, and a score thereof predicted outcome in large clinical patient data cohorts. Taken together, we provide proof of concept that intra-sample heterogeneity mimics inter-sample heterogeneity in AML. Stem cell disparities within a single sample allow insights into adverse characteristics of general importance for AML.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:37:02.261.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashokkumar Jayavelu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-26 23:39:11	ID requested
1	2022-05-25 09:12:14	announced
⏵ 2	2024-10-22 05:37:03	announced	2024-10-22: Updated project metadata.

10.1186/s13045-022-01232-4;

Zeller C, Richter D, Jurinovic V, Valtierra-Guti, é, rrez IA, Jayavelu AK, Mann M, Bagnoli JW, Hellmann I, Herold T, Enard W, Vick B, Jeremias I, Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients. J Hematol Oncol, 15(1):25(2022) [pubmed]

submitter keyword: AML, Resistance, Proteome, Stem Cells, PDX, Transcriptome

Prof.Dr.Matthias Mann
contact affiliation	MaxPlanck Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Ashokkumar Jayavelu
contact affiliation	Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry
contact email	jayavelu@biochem.mpg.de
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/2022/04/PXD026296

PRIDE project URI

• PRIDE
  1. PXD026296
     1. Label: PRIDE project
     2. Name: Adverse stem cell features in a single AML sample predict clinical outcome in AML patient cohorts