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Nat Genet DOI:10.1038/ng.3400

The genomic landscape of juvenile myelomonocytic leukemia.

Publication TypeJournal Article
Year of Publication2015
AuthorsStieglitz, E, Taylor-Weiner, AN, Chang, TY, Gelston, LC, Wang, Y-D, Mazor, T, Esquivel, E, Yu, A, Seepo, S, Olsen, SR, Rosenberg, M, Archambeault, SL, Abusin, G, Beckman, K, Brown, PA, Briones, M, Carcamo, B, Cooper, T, Dahl, GV, Emanuel, PD, Fluchel, MN, Goyal, RK, Hayashi, RJ, Hitzler, J, Hugge, C, Y Liu, L, Messinger, YH, Mahoney, DH, Monteleone, P, Nemecek, ER, Roehrs, PA, Schore, RJ, Stine, KC, Takemoto, CM, Toretsky, JA, Costello, JF, Olshen, AB, Stewart, C, Li, Y, Ma, J, Gerbing, RB, Alonzo, TA, Getz, G, Gruber, TA, Golub, TR, Stegmaier, K, Loh, ML
JournalNat Genet
Date Published2015 Nov
KeywordsAcute Disease, Child, Child, Preschool, Disease Progression, Disease-Free Survival, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Infant, Leukemia, Myeloid, Leukemia, Myelomonocytic, Juvenile, Male, Mutation, Prognosis, Signal Transduction

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.


Alternate JournalNat. Genet.
PubMed ID26457647
PubMed Central IDPMC4626387
Grant List1U10CA180899 / CA / NCI NIH HHS / United States
5P30CA082103 / CA / NCI NIH HHS / United States
5U10CA098543 / CA / NCI NIH HHS / United States
P30CA82103 / CA / NCI NIH HHS / United States
R01CA173085 / CA / NCI NIH HHS / United States
T32 CA128583 / CA / NCI NIH HHS / United States
T32CA128583 / CA / NCI NIH HHS / United States