| Literature DB >> 30926971 |
Ilaria Iacobucci1, Ji Wen1, Manja Meggendorfer2, John K Choi1, Lei Shi3, Stanley B Pounds3, Catherine L Carmichael4, Katherine E Masih1, Sarah M Morris1, R Coleman Lindsley5, Laura J Janke1, Thomas B Alexander6, Guangchun Song1, Chunxu Qu1, Yongjin Li7, Debbie Payne-Turner1, Daisuke Tomizawa8, Nobutaka Kiyokawa9, Marcus Valentine10, Virginia Valentine10, Giuseppe Basso11,12, Franco Locatelli13,14, Eric J Enemark15, Shirley K Y Kham16, Allen E J Yeoh16,17, Xiaotu Ma7, Xin Zhou7, Edgar Sioson7, Michael Rusch7, Rhonda E Ries18, Elliot Stieglitz19, Stephen P Hunger20, Andrew H Wei4,21,22, L Bik To23,24, Ian D Lewis24, Richard J D'Andrea25, Benjamin T Kile26,27, Anna L Brown25,28, Hamish S Scott25,28, Christopher N Hahn25,28, Paula Marlton29, Deqing Pei3, Cheng Cheng3, Mignon L Loh19, Benjamin L Ebert5, Soheil Meshinchi18, Torsten Haferlach2, Charles G Mullighan30.
Abstract
Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases and included recurrent mutations of ALK and NTRK1, the latter of which drives erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this high-risk leukemia.Entities:
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Year: 2019 PMID： 30926971 PMCID： PMC6828160 DOI： 10.1038/s41588-019-0375-1
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330