Please use this identifier to cite or link to this item: http://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
Rights: Copyright © 2019, Springer Nature
RMID: 0030112053
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
Appears in Collections:Medicine publications

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