Details

Autor(en) / Beteiligte

• Stieglitz, Elliot
• Mazor, Tali
• Olshen, Adam B.
• Geng, Huimin
• Gelston, Laura C.
• Akutagawa, Jon
• Lipka, Daniel B.
• Plass, Christoph
• Flotho, Christian
• Chehab, Farid F.
• Braun, Benjamin S.
• Costello, Joseph F.
• Loh, Mignon L.

Titel

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

Ist Teil von

• Nature communications, 2017-12, Vol.8 (1), p.2127-8, Article 2127

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• 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. Juvenile myelomonocytic leukemia (JMML) is an aggressive disease with limited options for treatment. Here, the authors utilize DNA methylation based subgroups in JMML to predict clinical outcome.