Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia

Abstract: Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in JMML vary markedly from spontaneous resolution to rapid relapse after hematopoietic stem cell transplantation. Here, we hypothesized that DNA methylation patterns would help predict disease outcome and therefore performed genome-wide DNA methylation profiling in a cohort of 39 patients. Unsupervised hierarchical clustering identifies three clusters of patients. Importantly, these clusters differ significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival. These findings were validated in an independent cohort of 40 patients. Notably, all but one of 14 patients experiencing spontaneous resolution cluster together and closer to 22 healthy controls than to other JMML cases. Thus, we show that DNA methylation patterns in JMML are predictive of outcome and can identify the patients most likely to experience spontaneous resolution

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Nature communications. - 8 (2017) , 2127, ISSN: 2041-1723

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
Stieglitz, Elliot
Mazor, Tali
Olshen, Adam B.
Geng, Huimin
Gelston, Laura C.
Akutagawa, Jon
Lipka, Daniel
Plass, Christoph
Flotho, Christian
Chehab, Farid F.
Braun, Benjamin S.
Costello, Joseph F.
Loh, Mignon L.

DOI
10.1038/s41467-017-02178-9
URN
urn:nbn:de:bsz:25-freidok-1438202
Rechteinformation
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:49 MEZ

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  • 2019

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