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Unified classification and risk-stratification in Acute Myeloid Leukemia

Tazi, Yanis, Arango-Ossa, Juan E., Zhou, Yangyu, Bernard, Elsa, Thomas, Ian, Gilkes, Amanda, Freeman, Sylvie, Pradat, Yoann, Johnson, Sean J., Hills, Robert, Dillon, Richard, Levine, Max F., Leongamornlert, Daniel, Butler, Adam, Ganser, Arnold, Bullinger, Lars, Döhner, Konstanze, Ottmann, Oliver, Adams, Richard, Döhner, Hartmut, Campbell, Peter J., Burnett, Alan K., Dennis, Michael, Russell, Nigel H., Devlin, Sean M., Huntly, Brian J. P. and Papaemmanuil, Elli 2022. Unified classification and risk-stratification in Acute Myeloid Leukemia. Nature Communications 13 (1) , 4622. 10.1038/s41467-022-32103-8

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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: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Research
ISSN: 2041-1723
Funders: CRUK
Date of First Compliant Deposit: 11 August 2022
Date of Acceptance: 11 July 2022
Last Modified: 12 Aug 2022 09:04
URI: https://orca.cardiff.ac.uk/id/eprint/151811

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