Title

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

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

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