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dc.contributor.authorForgione, M.O.-
dc.contributor.authorMcClure, B.J.-
dc.contributor.authorEadie, L.N.-
dc.contributor.authorYeung, D.T.-
dc.contributor.authorWhite, D.L.-
dc.identifier.citationCancer Letters, 2019; 469:410-418-
dc.description.abstractKMT2A rearranged (KMT2Ar) acute lymphoblastic leukaemia (ALL) is a high-risk genomic subtype, with long-term survival rates of less than 60% across all age groups. These cases present a complex clinical challenge, with a high incidence in infants, high-risk clinical features and propensity for aggressive relapse. KMT2A rearrangements are highly pathogenic leukaemic drivers, reflected by the high incidence of KMT2Ar ALL in infants, who carry few leukaemia-associated cooperative mutations. However, transgenic murine models of KMT2Ar ALL typically exhibit long latency and mature or mixed phenotype, and fail to recapitulate the aggressive disease observed clinically. Next-generation sequencing has revealed that KMT2Ar ALL also occurs in adolescents and adults, and potentially cooperative genomic lesions such as PI3K-RAS pathway variants are present in KMT2Ar patients of all ages. This review addresses the aetiology of KMT2Ar ALL, with a focus on the cell of origin and mutational landscape, and how genomic profiling of KMT2Ar ALL patients in the era of next-generation sequencing demonstrates that KMT2Ar ALL is a complex heterogenous disease. Ultimately, understanding the underlying biology of KMT2Ar ALL will be important in improving long-term outcomes for these high-risk patients.-
dc.description.statementofresponsibilityMichelle O.Forgione, Barbara J.McClure, Laura N.Eadie, David T.Yeung, Deborah L.White-
dc.rightsCrown Copyright © 2019 Published by Elsevier B.V. All rights reserved.-
dc.subjectMixed lineage leukemia-
dc.subjectadult acute lymphoblastic leukemia-
dc.subjectleukemia etiology-
dc.titleKMT2A rearranged acute lymphoblastic leukaemia: unravelling the genomic complexity and heterogeneity of this high-risk disease-
dc.typeJournal article-
dc.identifier.orcidForgione, M.O. [0000-0002-7020-7440]-
dc.identifier.orcidMcClure, B.J. [0000-0002-5201-4127]-
dc.identifier.orcidEadie, L.N. [0000-0003-1912-7602]-
dc.identifier.orcidYeung, D.T. [0000-0002-7558-9927]-
dc.identifier.orcidWhite, D.L. [0000-0003-4844-333X]-
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