PXD029216

PXD029216 is an original dataset announced via ProteomeXchange.

Title	Proteogenomic Characterization of Highly Enriched Viable Leukemic Blasts in Acute Myeloid Leukemia: A SWOG Report
Description	AML is a molecularly heterogenous disease that harbors multiple genomic, epigenomic, and transcriptomic abnormalities. Despite the use of newer therapeutic agents and identification of multiple prognostic markers, most patients with AML still relapse or succumb to their disease. Therefore, understanding biological factors especially at protein level that determine relapse is of major clinical interest in AML. Few studies have examined the global proteome in AML. Therefore, we have developed an integrated approach utilizing mass spectrometry-based proteomics and leveraging next generation RNA sequencing (RNAseq) to identify novel protein biomarkers associated with clinical outcome in a homogeneous population of undifferentiated viable leukemic blasts (uVLBs) from AML patients (Discovery cohort, n=27). Analyses identified 6761 unique proteins, with 238 and 460 proteins significantly associated with complete response (CR) and overall survival (OS), respectively. There was modest overlap between the prognostically significant transcript and protein biomarkers. We also were able to identify and quantify aberrant proteins arising from genomic mutations such as NPM1 and RUNX1. For validation of prognostic associations, TMT-based LC-MS/MS quantified protein expression across pooled patients from an independent patient cohort (validation cohort) and analyses examined the prognostic significance of the 238 proteins from the SWOG analyses associated with CR. Thirteen of the most promising candidates were significantly associated with CR prognosis, many of which are associated with cancer biology. Together, these studies show the feasibility and biological importance of examining the proteome in uVLBs. Studies examining for biomarkers in the proteome may be a powerful tool to uncover novel prognostic biomarkers that would otherwise not be identified by examining the genome or transcriptome. Furthermore, the multi-omics approach can be used to confirm the translation of potential neoantigens into actionable protein targets, which may lead to more cost-effective mechanisms for the development of innovative adoptive immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:53:28.519.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jacob Kennedy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-19 01:48:40	ID requested
⏵ 1	2025-05-06 12:53:29	announced

10.1002/jha2.1041;

Naru J, Othus M, Lin C, Biernacki MA, Bleakley M, Chauncey TR, Erba HP, Fang M, Fitzgibbon MP, Gafken PR, Ivey RG, Kennedy JJ, Lorentzen TD, Meshinchi S, Moseley A, Pogosova-Agadjanyan EL, Liu VM, Radich JP, Voytovich UJ, Wang P, Whiteaker JR, Willman CL, Wu F, Paulovich AG, Stirewalt DL, Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report. EJHaem, 5(6):1243-1251(2024) [pubmed]

submitter keyword: Human, TMT, SILAC, FACS, fractionation, AML, LC-MS/MS

Derek Stirewalt
contact affiliation	Clinical Research Division, Fred Hutchinson Cancer Center, USA
contact email	dstirewa@fredhutch.org
lab head
Jacob Kennedy
contact affiliation	Fred Hutchinson Cancer Research Center
contact email	jkennedy@fhcrc.org
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/2025/05/PXD029216

PRIDE project URI

• PRIDE
  1. PXD029216
     1. Label: PRIDE project
     2. Name: Proteogenomic Characterization of Highly Enriched Viable Leukemic Blasts in Acute Myeloid Leukemia: A SWOG Report