The genomic landscape of juvenile myelomonocytic leukemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-11

AUTHORS

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 Emanuel, Mark 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

ABSTRACT

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. More... »

PAGES

1326-1333

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3400

DOI

http://dx.doi.org/10.1038/ng.3400

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046661438

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26457647


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