The Genomic Landscape of Juvenile Myelomonocytic Leukemia.
Publication/Presentation Date
11-1-2015
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.
Volume
47
Issue
11
First Page
1326
Last Page
1333
ISSN
1546-1718
Published In/Presented At
Stieglitz, E., Taylor-Weiner, A. N., Chang, T. Y., Gelston, L. C., Wang, Y., Mazor, T., & ... Loh, M. L. (2015). The genomic landscape of juvenile myelomonocytic leukemia. Nature Genetics, 47(11), 1326-1333. doi:10.1038/ng.3400
Disciplines
Hematology | Medical Sciences | Medical Specialties | Medicine and Health Sciences | Oncology
PubMedID
26457647
Department(s)
Department of Medicine, Hematology-Medical Oncology Division
Document Type
Article