The genomic landscape of juvenile myelomonocytic leukemia.
Submitted by Eneida R Nemecek on
Title | The genomic landscape of juvenile myelomonocytic leukemia. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Stieglitz, E, Taylor-Weiner, AN, Chang, TY, Gelston, LC, Wang, Y-D, Mazor, T, Esquivel, E, Yu, A, Seepo, S, Olsen, S, 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, T, Golub, T, Stegmaier, K, Loh, ML |
Journal | Nat Genet |
Volume | 47 |
Issue | 11 |
Pagination | 1326-1333 |
Date Published | 2015 Nov |
ISSN | 1546-1718 |
Keywords | Acute 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 |
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. |
DOI | 10.1038/ng.3400 |
Alternate Journal | Nat. Genet. |
PubMed ID | 26457647 |
PubMed Central ID | PMC4626387 |
Grant List | 5U10CA098543 / CA / NCI NIH HHS / United States P30 CA082103 / CA / NCI NIH HHS / United States 5P30CA082103 / CA / NCI NIH HHS / United States P30 CA021765 / CA / NCI NIH HHS / United States T32CA128583 / CA / NCI NIH HHS / United States U10 CA098543 / CA / NCI NIH HHS / United States 1U10CA180899 / CA / NCI NIH HHS / United States U10 CA180899 / CA / NCI NIH HHS / United States R01CA173085 / CA / NCI NIH HHS / United States T32 CA128583 / CA / NCI NIH HHS / United States P30CA82103 / CA / NCI NIH HHS / United States R01 CA173085 / CA / NCI NIH HHS / United States |