dc.contributor.author |
Rücker, Frank G. |
dc.contributor.author |
Du, Ling |
dc.contributor.author |
Luck, Tamara J. |
dc.contributor.author |
Benner, Axel |
dc.contributor.author |
Krzykalla, Julia |
dc.contributor.author |
Gathmann, Insa |
dc.contributor.author |
Voso, Maria Teresa |
dc.contributor.author |
Amadori, Sergio |
dc.contributor.author |
Prior, Thomas W. |
dc.contributor.author |
Brandwein, Joseph M. |
dc.contributor.author |
Appelbaum, Frederick |
dc.contributor.author |
Medeiros, Bruno |
dc.contributor.author |
Tallman, Martin S. |
dc.contributor.author |
Savoie, Lynn |
dc.contributor.author |
Sierra, Jorge |
dc.contributor.author |
Pallaud, Celine |
dc.contributor.author |
Sanz, Miguel A.. |
dc.contributor.author |
Jansen, Joop H. |
dc.contributor.author |
Niederwieser, Dietger |
dc.contributor.author |
Fischer, Thomas |
dc.contributor.author |
Ehninger, Gerhard |
dc.contributor.author |
Heuser, Michael |
dc.contributor.author |
Ganser, Arnold |
dc.contributor.author |
Bullinger, Lars |
dc.contributor.author |
Larson, Richard A. |
dc.contributor.author |
Bloomfield, Clara D. |
dc.contributor.author |
Stone, Richard M. |
dc.contributor.author |
Döhner, Hartmut |
dc.contributor.author |
Thiede, Christian |
dc.contributor.author |
Döhner, Konstanze |
dc.contributor.author |
Universitat Autònoma de Barcelona |
dc.date |
2021 |
dc.identifier |
https://ddd.uab.cat/record/250440 |
dc.identifier |
urn:10.1038/s41375-021-01323-0 |
dc.identifier |
urn:oai:ddd.uab.cat:250440 |
dc.identifier |
urn:pmcid:PMC8727286 |
dc.identifier |
urn:pmc-uid:8727286 |
dc.identifier |
urn:pmid:34316017 |
dc.identifier |
urn:articleid:14765551v36p90 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:8727286 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Leukemia ; Vol. 36 (july 2021), p. 90-99 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.title |
Molecular landscape and prognostic impact of FLT3 -ITD insertion site in acute myeloid leukemia : RATIFY study results |
dc.type |
Article |
dc.description.abstract |
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. |