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000170080 1001_ $$aRücker, Frank G$$b0
000170080 245__ $$aMolecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results.
000170080 260__ $$aLondon$$bSpringer Nature$$c2022
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000170080 500__ $$a2022 Jan;36(1):90-99
000170080 520__ $$aIn acute myeloid leukemia (AML) internal tandem duplications of the FLT3 gene (FLT3-ITD) are associated with poor prognosis. Retrospectively, we investigated the prognostic and predictive impact of FLT3-ITD insertion site (IS) in 452 patients randomized within the RATIFY trial, which evaluated midostaurin additionally to intensive chemotherapy. Next-generation sequencing identified 908 ITDs, with 643 IS in the juxtamembrane domain (JMD) and 265 IS in the tyrosine kinase domain-1 (TKD1). According to IS, patients were categorized as JMDsole (n = 251, 55%), JMD and TKD1 (JMD/TKD1; n = 117, 26%), and TKD1sole (n = 84, 19%). While clinical variables did not differ among the 3 groups, NPM1 mutation was correlated with JMDsole (P = 0.028). Overall survival (OS) differed significantly, with estimated 4-year OS probabilities of 0.44, 0.50, and 0.30 for JMDsole, JMD/TKD1, and TKD1sole, respectively (P = 0.032). Multivariate (cause-specific) Cox models for OS and cumulative incidence of relapse using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable identified TKD1sole as unfavorable and HCT as favorable factors. In addition, Midostaurin exerted a significant benefit only for JMDsole. Our results confirm the distinct molecular heterogeneity of FLT3-ITD and the negative prognostic impact of TKD1 IS in AML that was not overcome by midostaurin.
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000170080 7001_ $$aDu, Ling$$b1
000170080 7001_ $$0P:(DE-HGF)0$$aLuck, Tamara J$$b2
000170080 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b3$$udkfz
000170080 7001_ $$0P:(DE-He78)5a7a75d1b29b770f98f1bb2062fc3df9$$aKrzykalla, Julia$$b4$$udkfz
000170080 7001_ $$aGathmann, Insa$$b5
000170080 7001_ $$00000-0002-6164-4761$$aVoso, Maria Teresa$$b6
000170080 7001_ $$aAmadori, Sergio$$b7
000170080 7001_ $$aPrior, Thomas W$$b8
000170080 7001_ $$aBrandwein, Joseph M$$b9
000170080 7001_ $$aAppelbaum, Frederick R$$b10
000170080 7001_ $$00000-0001-6972-8137$$aMedeiros, Bruno C$$b11
000170080 7001_ $$aTallman, Martin S$$b12
000170080 7001_ $$aSavoie, Lynn$$b13
000170080 7001_ $$aSierra, Jorge$$b14
000170080 7001_ $$aPallaud, Celine$$b15
000170080 7001_ $$00000-0003-1489-1177$$aSanz, Miguel A$$b16
000170080 7001_ $$aJansen, Joop H$$b17
000170080 7001_ $$00000-0002-4737-1103$$aNiederwieser, Dietger$$b18
000170080 7001_ $$aFischer, Thomas$$b19
000170080 7001_ $$aEhninger, Gerhard$$b20
000170080 7001_ $$00000-0001-5318-9044$$aHeuser, Michael$$b21
000170080 7001_ $$aGanser, Arnold$$b22
000170080 7001_ $$aBullinger, Lars$$b23
000170080 7001_ $$00000-0001-9168-3203$$aLarson, Richard A$$b24
000170080 7001_ $$00000-0001-5465-7591$$aBloomfield, Clara D$$b25
000170080 7001_ $$aStone, Richard M$$b26
000170080 7001_ $$aDöhner, Hartmut$$b27
000170080 7001_ $$00000-0003-1241-2048$$aThiede, Christian$$b28
000170080 7001_ $$00000-0002-2261-9862$$aDöhner, Konstanze$$b29
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