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Supplementary Table from Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression

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posted on 2023-04-04, 01:40 authored by Andrew J. Menssen, Ajay Khanna, Christopher A. Miller, Sridhar Nonavinkere Srivatsan, Gue Su Chang, Jin Shao, Joshua Robinson, Michele O'Laughlin, Catrina C. Fronick, Robert S. Fulton, Kimberly Brendel, Sharon E. Heath, Raya Saba, John S. Welch, David H. Spencer, Jacqueline E. Payton, Peter Westervelt, John F. DiPersio, Daniel C. Link, Matthew J. Schuelke, Meagan A. Jacoby, Eric J. Duncavage, Timothy J. Ley, Matthew J. Walter
Supplementary Table from Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression

Funding

NCI

SPORE

Siteman Cancer Center

The Foundation for Barnes-Jewish Hospital Cancer Frontier Fund

NCI Career Enhancement Program

Washington University Institute of Clinical and Translational Sciences

National Center for Advancing Translational Sciences

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National Center for Advancing Translational Sciences of the National Institutes of Health

NCI Research Specialist Award

NCI Cancer Center Support Grant

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ARTICLE ABSTRACT

Progression from myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (AML) is associated with the acquisition and expansion of subclones. Our understanding of subclone evolution during progression, including the frequency and preferred order of gene mutation acquisition, remains incomplete. Sequencing of 43 paired MDS and secondary AML samples identified at least one signaling gene mutation in 44% of MDS and 60% of secondary AML samples, often below the level of standard sequencing detection. In addition, 19% of MDS and 47% of secondary AML patients harbored more than one signaling gene mutation, almost always in separate, coexisting subclones. Signaling gene mutations demonstrated diverse patterns of clonal evolution during disease progression, including acquisition, expansion, persistence, and loss of mutations, with multiple patterns often coexisting in the same patient. Multivariate analysis revealed that MDS patients who had a signaling gene mutation had a higher risk of AML progression, potentially providing a biomarker for progression. Subclone expansion is a hallmark of progression from MDS to secondary AML. Subclonal signaling gene mutations are common at MDS (often at low levels), show complex and convergent patterns of clonal evolution, and are associated with future progression to secondary AML.See related article by Guess et al., p. 316 (33).See related commentary by Romine and van Galen, p. 270.This article is highlighted in the In This Issue feature, p. 265

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