Home > Publications database > Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results. > print

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024 7 _ |a 10.1038/s41375-021-01323-0
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024 7 _ |a pmid:34316017
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024 7 _ |a 0887-6924
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024 7 _ |a 1476-5551
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037 _ _ |a DKFZ-2021-01743
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Rücker, Frank G
|b 0
245 _ _ |a Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results.
260 _ _ |a London
|c 2022
|b Springer Nature
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336 7 _ |a Journal Article
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500 _ _ |a 2022 Jan;36(1):90-99
520 _ _ |a In 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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700 1 _ |a Du, Ling
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700 1 _ |a Luck, Tamara J
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700 1 _ |a Benner, Axel
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700 1 _ |a Krzykalla, Julia
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700 1 _ |a Gathmann, Insa
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700 1 _ |a Voso, Maria Teresa
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700 1 _ |a Amadori, Sergio
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700 1 _ |a Prior, Thomas W
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700 1 _ |a Brandwein, Joseph M
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700 1 _ |a Appelbaum, Frederick R
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700 1 _ |a Medeiros, Bruno C
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700 1 _ |a Tallman, Martin S
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700 1 _ |a Savoie, Lynn
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700 1 _ |a Sierra, Jorge
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700 1 _ |a Pallaud, Celine
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700 1 _ |a Sanz, Miguel A
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700 1 _ |a Jansen, Joop H
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700 1 _ |a Niederwieser, Dietger
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700 1 _ |a Fischer, Thomas
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700 1 _ |a Ehninger, Gerhard
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700 1 _ |a Heuser, Michael
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700 1 _ |a Ganser, Arnold
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700 1 _ |a Bullinger, Lars
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700 1 _ |a Larson, Richard A
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700 1 _ |a Bloomfield, Clara D
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700 1 _ |a Stone, Richard M
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700 1 _ |a Döhner, Hartmut
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700 1 _ |a Thiede, Christian
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700 1 _ |a Döhner, Konstanze
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