Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes

Jasmijn D.E. De Rooij, Cristyn Branstetter, Jing Ma, Yongjin Li, Michael P. Walsh, Jinjun Cheng, Askar Obulkasim, Jinjun Dang, John Easton, Lonneke J. Verboon, Heather L. Mulder, Martin Zimmermann, Cary Koss, Pankaj Gupta, Michael Edmonson, Michael Rusch, Joshua Yew Suang Lim, Katarina Reinhardt, Martina Pigazzi, Guangchun SongAllen Eng Juh Yeoh, Lee Yung Shih, Der Cherng Liang, Stephanie Halene, Diane S. Krause, Jinghui Zhang, James R. Downing, Franco Locatelli, Dirk Reinhardt, Marry M. Van Den Heuvel-Eibrink, C. Michel Zwaan, Maarten Fornerod, Tanja A. Gruber

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

142 Citaten (Scopus)

Samenvatting

Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) in which cells morphologically resemble abnormal megakaryoblasts. While rare in adults, AMKL accounts for 4-15% of newly diagnosed childhood AML cases. AMKL in individuals without Down syndrome (non-DS-AMKL) is frequently associated with poor clinical outcomes. Previous efforts have identified chimeric oncogenes in a substantial number of non-DS-AMKL cases, including RBM15-MKL1, CBFA2T3-GLIS2, KMT2A gene rearrangements, and NUP98-KDM5A. However, the etiology of 30-40% of cases remains unknown. To better understand the genomic landscape of non-DS-AMKL, we performed RNA and exome sequencing on specimens from 99 patients (75 pediatric and 24 adult). We demonstrate that pediatric non-DS-AMKL is a heterogeneous malignancy that can be divided into seven subgroups with varying outcomes. These subgroups are characterized by chimeric oncogenes with cooperating mutations in epigenetic and kinase signaling genes. Overall, these data shed light on the etiology of AMKL and provide useful information for the tailoring of treatment.

Originele taal-2Engels
Pagina's (van-tot)451-456
Aantal pagina's6
TijdschriftNature Genetics
Volume49
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 1 mrt. 2017

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