The genomic landscape of juvenile myelomonocytic leukemia

Elliot Stieglitz, Amaro N. Taylor-Weiner, Tiffany Y. Chang, Laura C. Gelston, Yong Dong Wang, Tali Mazor, Emilio Esquivel, Ariel Yu, Sara Seepo, Scott R. Olsen, Mara Rosenberg, Sophie L. Archambeault, Ghada Abusin, Kyle Beckman, Patrick A. Brown, Michael Briones, Benjamin Carcamo, Todd Cooper, Gary V. Dahl, Peter D. EmanuelMark N. Fluchel, Rakesh K. Goyal, Robert J. Hayashi, Johann Hitzler, Christopher Hugge, Y. Lucy Liu, Yoav H. Messinger, Donald H. Mahoney, Philip Monteleone, Eneida R. Nemecek, Philip A. Roehrs, Reuven J. Schore, Kimo C. Stine, Clifford M. Takemoto, Jeffrey A. Toretsky, Joseph F. Costello, Adam B. Olshen, Chip Stewart, Yongjin Li, Jing Ma, Robert B. Gerbing, Todd A. Alonzo, Gad Getz, Tanja A. Gruber, Todd R. Golub, Kimberly Stegmaier, Mignon L. Loh

Research output: Contribution to journalArticlepeer-review

138 Scopus citations


Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription. Notably, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.

Original languageEnglish (US)
Pages (from-to)1326-1333
Number of pages8
JournalNature genetics
Issue number11
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Genetics


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