Unified classification and risk-stratification in Acute Myeloid Leukemia

Tazi, Y. et al. (2022) Unified classification and risk-stratification in Acute Myeloid Leukemia. Nature Communications, 13, 4622. (doi: 10.1038/s41467-022-32103-8) (PMID:35941135) (PMCID:PMC9360033)

Abstract

Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow Minimal Residual Disease (MRD) negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool.

• Item Type: Articles
• Additional Information: E.P. is a Josie Robertson Investigator and is supported by the European Hematology Association, American Society of Hematology, Gabrielle’s Angels Foundation, V Foundation and The Geoffrey Beene Foundation and is a Damon Runyon Rachleff Innovator fellow. Work in the B.J.P.H. lab is funded by Cancer Research UK (C18680/A25508), the European Research Council (647685), MRC (MR-R009708-1), the Kay Kendall Leukemia Fund (KKL1243), the Wellcome Trust (205254/Z/16/Z) and the Cancer Research UK Cambridge Major Centre (C49940/A25117). This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), and was funded in part, by the Wellcome Trust who supported the Wellcome—MRC Cambridge Stem Cell Institute (203151/Z/16/Z).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Burnett, Professor Alan
• Authors: Tazi, Y., Arango-Ossa, J. E., Zhou, Y., Bernard, E., Thomas, I., Gilkes, A., Freeman, S., Pradat, Y., Johnson, S. J., Hills, R., Dillon, R., Levine, M. F., Leongamornlert, D., Butler, A., Ganser, A., Bullinger, L., Döhner, K., Ottmann, O., Adams, R., Döhner, H., Campbell, P. J., Burnett, A. K., Dennis, M., Russell, N. H., Devlin, S. M., Huntly, B. J. P., and Papaemmanuil, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © The Author(s) 2022
• First Published: First published in Nature Communications 13: 4622
• Publisher Policy: Reproduced under a Creative Commons licence