Epigenomic diagnosis and prognosis of Acute Myeloid Leukemia
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.
Article Details
Authors (29)
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
Jatinder K. Lamba