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https://hdl.handle.net/2440/119846
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Type: | Journal article |
Title: | Genomic subtyping and therapeutic targeting of acute erythroleukemia |
Author: | Iacobucci, I. Wen, J. Meggendorfer, M. Choi, J.K. Shi, L. Pounds, S.B. Carmichael, C.L. Masih, K.E. Morris, S.M. Lindsley, R.C. Janke, L.J. Alexander, T.B. Song, G. Qu, C. Li, Y. Payne-Turner, D. Tomizawa, D. Kiyokawa, N. Valentine, M. Valentine, V. et al. |
Citation: | Nature Genetics, 2019; 51(4):694-704 |
Publisher: | Springer Nature |
Issue Date: | 2019 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Ilaria Iacobucci … L. Bik To, Ian D. Lewis, Richard J. D’Andrea … Anna L. Brown, Hamish S. Scott, Christopher H. Hahn … Charles G. Mullighan |
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. |
Keywords: | Humans Leukemia, Erythroblastic, Acute Homeodomain Proteins Nuclear Proteins Prognosis Genomics Mutation Adolescent Adult Child Child, Preschool Infant Infant, Newborn Female Male Tumor Suppressor Protein p53 Myeloid-Lymphoid Leukemia Protein fms-Like Tyrosine Kinase 3 Young Adult Nucleophosmin |
Rights: | Copyright © 2019, Springer Nature |
DOI: | 10.1038/s41588-019-0375-1 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/516726 http://purl.org/au-research/grants/nhmrc/1016647 http://purl.org/au-research/grants/nhmrc/1113577 http://purl.org/au-research/grants/nhmrc/1063008 http://purl.org/au-research/grants/nhmrc/361646 |
Published version: | http://dx.doi.org/10.1038/s41588-019-0375-1 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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