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000291455 1001_ $$00000-0002-6601-3096$$aHernández-Sánchez, Alberto$$b0
000291455 245__ $$aRearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.
000291455 260__ $$aLondon$$bSpringer Nature$$c2024
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000291455 500__ $$a2024 Sep;38(9):1929-1937
000291455 520__ $$aBalanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.
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000291455 7001_ $$aGonzález, Teresa$$b1
000291455 7001_ $$aSobas, Marta$$b2
000291455 7001_ $$aSträng, Eric$$b3
000291455 7001_ $$00000-0003-4892-925X$$aCastellani, Gastone$$b4
000291455 7001_ $$aAbáigar, María$$b5
000291455 7001_ $$00000-0002-8857-9461$$aValk, Peter J M$$b6
000291455 7001_ $$00000-0002-7337-7218$$aVillaverde Ramiro, Ángela$$b7
000291455 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b8$$udkfz
000291455 7001_ $$00000-0003-3920-7490$$aMetzeler, Klaus H$$b9
000291455 7001_ $$aAzibeiro, Raúl$$b10
000291455 7001_ $$00000-0002-0811-0824$$aTettero, Jesse M$$b11
000291455 7001_ $$00000-0001-7908-0063$$aMartínez-López, Joaquín$$b12
000291455 7001_ $$aPratcorona, Marta$$b13
000291455 7001_ $$00000-0001-5294-6162$$aMartínez Elicegui, Javier$$b14
000291455 7001_ $$00000-0002-6362-4481$$aMills, Ken I$$b15
000291455 7001_ $$00000-0003-1241-2048$$aThiede, Christian$$b16
000291455 7001_ $$00000-0002-2767-8191$$aSanz, Guillermo$$b17
000291455 7001_ $$00000-0002-2261-9862$$aDöhner, Konstanze$$b18
000291455 7001_ $$00000-0001-5318-9044$$aHeuser, Michael$$b19
000291455 7001_ $$00000-0003-0196-2837$$aHaferlach, Torsten$$b20
000291455 7001_ $$00000-0003-1347-3360$$aTurki, Amin T$$b21
000291455 7001_ $$aReinhardt, Dirk$$b22
000291455 7001_ $$aSchulze-Rath, Renate$$b23
000291455 7001_ $$aBarbus, Martje$$b24
000291455 7001_ $$aHernández-Rivas, Jesús María$$b25
000291455 7001_ $$00000-0003-0312-161X$$aHuntly, Brian$$b26
000291455 7001_ $$aOssenkoppele, Gert$$b27
000291455 7001_ $$00000-0003-2116-5536$$aDöhner, Hartmut$$b28
000291455 7001_ $$00000-0002-5890-5510$$aBullinger, Lars$$b29
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