The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms

Jason R. Schwartz, Jing Ma, Jennifer Kamens, Tamara Westover, Michael P. Walsh, Samuel W. Brady, J. Robert Michael, Xiaolong Chen, Lindsey Montefiori, Guangchun Song, Gang Wu, Huiyun Wu, Cristyn Branstetter, Ryan Hiltenbrand, Michael F. Walsh, Kim E. Nichols, Jamie L. Maciaszek, Yanling Liu, Priyadarshini Kumar, John Easton, Scott Newman, Jeffrey E. Rubnitz, Charles G. Mullighan, Stanley Pounds, Jinghui Zhang, Tanja Gruber (), Xiaotu Ma () and Jeffery M. Klco ()
Additional contact information
Jason R. Schwartz: Vanderbilt University Medical Center, Department of Pediatrics
Jing Ma: St. Jude Children’s Research Hospital, Department of Pathology
Jennifer Kamens: Stanford University School of Medicine, Department of Pediatrics
Tamara Westover: St. Jude Children’s Research Hospital, Department of Pathology
Michael P. Walsh: St. Jude Children’s Research Hospital, Department of Pathology
Samuel W. Brady: St. Jude Children’s Research Hospital, Department of Computational Biology
J. Robert Michael: St. Jude Children’s Research Hospital, Department of Computational Biology
Xiaolong Chen: St. Jude Children’s Research Hospital, Department of Computational Biology
Lindsey Montefiori: St. Jude Children’s Research Hospital, Department of Pathology
Guangchun Song: St. Jude Children’s Research Hospital, Department of Pathology
Gang Wu: St. Jude Children’s Research Hospital, Department of Computational Biology
Huiyun Wu: St. Jude Children’s Research Hospital, Department of Biostatistics
Cristyn Branstetter: Arkansas Children’s Northwest Hospital, Department of Hematology/Oncology
Ryan Hiltenbrand: St. Jude Children’s Research Hospital, Department of Pathology
Michael F. Walsh: Memorial Sloan Kettering Cancer Center, Department of Pediatrics
Kim E. Nichols: St. Jude Children’s Research Hospital, Department of Oncology
Jamie L. Maciaszek: St. Jude Children’s Research Hospital, Department of Oncology
Yanling Liu: St. Jude Children’s Research Hospital, Department of Computational Biology
Priyadarshini Kumar: St. Jude Children’s Research Hospital, Department of Pathology
John Easton: St. Jude Children’s Research Hospital, Department of Computational Biology
Scott Newman: St. Jude Children’s Research Hospital, Department of Computational Biology
Jeffrey E. Rubnitz: St. Jude Children’s Research Hospital, Department of Oncology
Charles G. Mullighan: St. Jude Children’s Research Hospital, Department of Pathology
Stanley Pounds: St. Jude Children’s Research Hospital, Department of Biostatistics
Jinghui Zhang: St. Jude Children’s Research Hospital, Department of Computational Biology
Tanja Gruber: Stanford University School of Medicine, Department of Pediatrics
Xiaotu Ma: St. Jude Children’s Research Hospital, Department of Computational Biology
Jeffery M. Klco: St. Jude Children’s Research Hospital, Department of Pathology

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 84 pediatric tMN cases (tMDS: n = 28, tAML: n = 56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases are unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21255-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21255-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21255-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().