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Unified classification and risk-stratification in Acute Myeloid Leukemia

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Item Type:Article
Title:Unified classification and risk-stratification in Acute Myeloid Leukemia
Creators Name:Tazi, Y. and Arango-Ossa, J.E. and Zhou, Y. and Bernard, E. and Thomas, I. and Gilkes, A. and Freeman, S. and Pradat, Y. and Johnson, S.J. and Hills, R. and Dillon, R. and Levine, M.F. and Leongamornlert, D. and Butler, A. and Ganser, A. and Bullinger, L. and Döhner, K. and Ottmann, O. and Adams, R. and Döhner, H. and Campbell, P.J. and Burnett, A.K. and Dennis, M. and Russell, N.H. and Devlin, S.M. and Huntly, B.J.P. and Papaemmanuil, E.
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.
Keywords:Acute Myeloid Leukaemia, Cancer Genomics
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:13
Number:1
Page Range:4622
Date:8 August 2022
Official Publication:https://doi.org/10.1038/s41467-022-32103-8
PubMed:View item in PubMed

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