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Blood. 2015 Jan 15;125(3):516-24. doi: 10.1182/blood-2014-09-601690. Epub 2014 Nov 13.

Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia.

Author information

1
Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA;
2
Bio-Rad Laboratories, Hercules, CA;
3
Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA;
4
Center for Advanced Technology, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA;
5
Broad Institute, Cambridge, MA;
6
Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR;
7
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN;
8
Children's Oncology Group, Monrovia, CA;
9
Keck School of Medicine, University of Southern California, Los Angeles, CA; and.
10
Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.

Abstract

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of childhood associated with a poor prognosis. Recently, massively parallel sequencing has identified recurrent mutations in the SKI domain of SETBP1 in a variety of myeloid disorders. These lesions were detected in nearly 10% of patients with JMML and have been characterized as secondary events. We hypothesized that rare subclones with SETBP1 mutations are present at diagnosis in a large portion of patients who relapse, but are below the limits of detection for conventional deep sequencing platforms. Using droplet digital polymerase chain reaction, we identified SETBP1 mutations in 17/56 (30%) of patients who were treated in the Children's Oncology Group sponsored clinical trial, AAML0122. Five-year event-free survival in patients with SETBP1 mutations was 18% ± 9% compared with 51% ± 8% for those without mutations (P = .006).

PMID:
25395418
PMCID:
PMC4296011
DOI:
10.1182/blood-2014-09-601690
[Indexed for MEDLINE]
Free PMC Article

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