Epigenomic diagnosis and prognosis of Acute Myeloid Leukemia

Francisco Marchi, Vivek M. Shastri, Richard J. Marrero, Nam H. K. Nguyen, Antonella Öttl, Ann-Kathrin Schade, Marieke Landwehr, Olga Krali, Jessica Nordlund, Matin Ghavami, Fernando Sckaff, Vikash K. Mansinghka, Xueyuan Cao, William Slayton, Petr Starostik, Christopher R. Cogle, Raul C. Ribeiro, Jeffrey E. Rubnitz, Jeffery Klco, Abdelrahman Elsayed, Alan S. Gamis, Timothy J. Triche, Rhonda Ries, E. Anders Kolb, Richard Aplenc, Todd Alonzo, Stanley Pounds, Soheil Meshinchi and Jatinder K. Lamba ()
Additional contact information
Francisco Marchi: College of Pharmacy, University of Florida
Vivek M. Shastri: College of Pharmacy, University of Florida
Richard J. Marrero: College of Pharmacy, University of Florida
Nam H. K. Nguyen: College of Pharmacy, University of Florida
Antonella Öttl: College of Pharmacy, University of Florida
Ann-Kathrin Schade: College of Pharmacy, University of Florida
Marieke Landwehr: College of Pharmacy, University of Florida
Olga Krali: Uppsala University
Jessica Nordlund: Uppsala University
Matin Ghavami: MIT
Fernando Sckaff: College of Pharmacy, University of Florida
Vikash K. Mansinghka: MIT
Xueyuan Cao: University of Tennessee Health Science Center
William Slayton: University of Florida
Petr Starostik: University of Florida Health Cancer Center
Christopher R. Cogle: University of Florida Health Cancer Center
Raul C. Ribeiro: St. Jude Children’s Research Hospital
Jeffrey E. Rubnitz: St. Jude Children’s Research Hospital
Jeffery Klco: St. Jude Children’s Research Hospital
Abdelrahman Elsayed: St. Jude Children’s Research Hospital
Alan S. Gamis: Children’s Mercy Kansas City
Timothy J. Triche: Van Andel Institute
Rhonda Ries: Fred Hutchinson Cancer Center
E. Anders Kolb: Leukemia & Lymphoma Society
Richard Aplenc: Perelman School of Medicine at the University of Pennsylvania
Todd Alonzo: University of Southern California Keck School of Med
Stanley Pounds: St. Jude Children’s Research Hospital
Soheil Meshinchi: Fred Hutchinson Cancer Center
Jatinder K. Lamba: College of Pharmacy, University of Florida

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients’ whole genomes and epigenomes. Clinical validation on patient samples confirms high concordance between epigenomic signatures and genomic lesions, though uniquely rare karyotypes remained challenging due to limited available training data. These results unveil the potential for increased affordability, speed, and accuracy for patients in need of complex molecular diagnosis and prognosis.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62005-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62005-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62005-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().