| Literature DB >> 28112737 |
Jasmijn D E de Rooij1, Cristyn Branstetter2, Jing Ma3, Yongjin Li4, Michael P Walsh3, Jinjun Cheng3, Askar Obulkasim1, Jinjun Dang2, John Easton4, Lonneke J Verboon1, Heather L Mulder4, Martin Zimmermann5, Cary Koss2, Pankaj Gupta4, Michael Edmonson4, Michael Rusch4, Joshua Yew Suang Lim6, Katarina Reinhardt7, Martina Pigazzi8, Guangchun Song3, Allen Eng Juh Yeoh6,9, Lee-Yung Shih10, Der-Cherng Liang11, Stephanie Halene12, Diane S Krause13, Jinghui Zhang4, James R Downing3, Franco Locatelli14, Dirk Reinhardt7, Marry M van den Heuvel-Eibrink1,15, C Michel Zwaan1, Maarten Fornerod1, Tanja A Gruber2,3.
Abstract
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.Entities:
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Year: 2017 PMID： 28112737 PMCID： PMC5687824 DOI： 10.1038/ng.3772
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330