Title

The Genomic Landscape of Juvenile Myelomonocytic Leukemia.

Authors

Elliot Stieglitz, Benioff Children's Hospital, University of California
Amaro N. Taylor-Weiner, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Tiffany Y. Chang, Benioff Children's Hospital, University of California, San Francisco, CA.
Laura C. Gelston, Benioff Children's Hospital, University of California, San Francisco, San Francisco
Yong-Dong Wang, St. Jude Children's Research Hospital, Memphis, Tennessee
Tali Mazor, University of California, San Francisco, San Francisco, California
Emilio Esquivel, Benioff Children's Hospital, University of California, San Francisco, California
Ariel Yu, Benioff Children's Hospital, University of California, San Francisco, California
Sara Seepo, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Scott R. Olsen, St. Jude Children's Research Hospital, Memphis, Tennessee
Mara Rosenberg, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Sophie L Archambeault, Benioff Children's Hospital, University of California, San Francisco, California
Ghada Abusin, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa
Kyle Beckman, Benioff Children's Hospital, University of California, San Francisco, California
Patrick A. Brown, Johns Hopkins Hospital, Baltimore, Maryland
Michael Briones, Emory University School of Medicine, Aflac Cancer and Blood Disorder Center, Atlanta, Georgia
Benjamin Carcamo, Texas Tech University, El Paso, Texas
Todd Cooper, Seattle Children's Hospital, Seattle, Washington
Gary V. Dahl, Stanford School of Medicine, Stanford, California
Peter D. Emanuel, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Mark N. Fluchel, Hematology Oncology, University of Utah, Salt Lake City, Utah
Rakesh K. Goyal, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
Robert J. Hayashi, Washington University School of Medicine, St. Louis, Missouri
Johann Hitzler, The Hospital for Sick Children, Toronto, Ontario, Canada
Christopher Hugge, SSM Cardinal Glennon Children's Medical Center, St. Louis, Missouri
Y Lucy Liu, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Yoav H Messinger, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota
Donald H Mahoney, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas
Philip Monteleone MD, Lehigh Valley Health NetworkFollow
Eneida R. Nemecek, Pediatric Bone Marrow Transplant Program, Oregon Health and Science University, Portland, Oregon
Philip A Roehrs, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Reuven J Schore, Children's National Medical Center, Washington, DC
Kimo C. Stine, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Clifford M. Takemoto, Johns Hopkins Hospital, Baltimore, Maryland
Jeffrey A. Toretsky, eorgetown University, Washington, DC, USA.; Department of Oncology, Georgetown University, Washington, DC
Joseph F. Costello, University of California, San Francisco, San Francisco, California
Adam B. Olshen, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
Chip Stewart, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Yongjin Li, St. Jude Children's Research Hospital, Memphis, Tennessee
Jing Ma, St. Jude Children's Research Hospital, Memphis, Tennessee
Robert B. Gerbing, Children's Oncology Group, Monrovia, California
Todd A. Alonzo, Keck School of Medicine, University of Southern California, Los Angeles, California
Gad Getz, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Tanja A. Gruber, St. Jude Children's Research Hospital, Memphis, Tennessee
Todd R. Golub, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Kimberly Stegmaier, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
Mignon L Loh, Benioff Children's Hospital, University of California, San Francisco, San Francisco, California

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