Dataset Information

Proteogenomic Characterization of Highly Enriched Viable Leukemic Blasts in Acute Myeloid Leukemia: A SWOG Report

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Jacob Kennedy

LAB HEAD: Derek Stirewalt

PROVIDER: PXD029216 | Pride | 2025-05-06

REPOSITORIES: Pride

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			Action	DRS
	AML1001_Blast_BM_2D_F01.raw	Raw
	AML1001_Blast_BM_2D_F02.raw	Raw
	AML1001_Blast_BM_2D_F03.raw	Raw
	AML1001_Blast_BM_2D_F04.raw	Raw
	AML1001_Blast_BM_2D_F05.raw	Raw

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Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report.

Naru Jasmine J Othus Megan M Lin ChenWei C Biernacki Melinda A MA Bleakley Marie M Chauncey Thomas R TR Erba Harry P HP Fang Min M Fitzgibbon Matthew P MP Gafken Phillip R PR Ivey Richard G RG Kennedy Jacob J JJ Lorentzen Travis D TD Meshinchi Soheil S Moseley Anna A Pogosova-Agadjanyan Era L EL Liu Vivian M VM Radich Jerald P JP Voytovich Uliana J UJ Wang Pei P Whiteaker Jeffrey R JR Willman Cheryl L CL Wu Feinan F Paulovich Amanda G AG Stirewalt Derek L DL

EJHaem 20241025 6

<h4>Introduction</h4>Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells. Several studies have examined the global proteome in bulk mononuclear cells (MNCs) from AML specimens, which are comprised a heterogenous population of cells at various stages of d ...[more]

PMID: 39691254

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