BACKGROUND: FLT3 mutation is present in 25-30% of all acute myeloid leukemias (AML), and it is associated with adverse outcome. FLT3 inhibitors have shown improved survival results in AML both as upfront treatment and in relapsed/refractory disease. Curiously, a variable proportion of wild-type FLT3 patients also responded to these drugs. METHODS: We analyzed 6 different transcriptomic datasets of AML cases. Differential expression between mutated and wild-type FLT3 AMLs was performed with the Wilcoxon-rank sum test. Hierarchical clustering was used to identify FLT3-mutation like AMLs. Finally, enrichment in recurrent mutations was performed with the Fisher's test. RESULTS: A FLT3 mutation-like gene expression pattern was identified among wild-type FLT3 AMLs. This pattern was highly enriched in NPM1 and DNMT3A mutants, and particularly in combined NPM1/DNMT3A mutants. CONCLUSIONS: We identified a FLT3 mutation-like gene expression pattern in AML which was highly enriched in NPM1 and DNMT3A mutations. Future analysis about the predictive role of this biomarker among wild-type FLT3 patients treated with FLT3 inhibitors is envisaged.
BACKGROUND: FLT3 mutation is present in 25-30% of all acute myeloid leukemias (AML), and it is associated with adverse outcome. FLT3 inhibitors have shown improved survival results in AML both as upfront treatment and in relapsed/refractory disease. Curiously, a variable proportion of wild-type FLT3 patients also responded to these drugs. METHODS: We analyzed 6 different transcriptomic datasets of AML cases. Differential expression between mutated and wild-type FLT3 AMLs was performed with the Wilcoxon-rank sum test. Hierarchical clustering was used to identify FLT3-mutation like AMLs. Finally, enrichment in recurrent mutations was performed with the Fisher's test. RESULTS: A FLT3 mutation-like gene expression pattern was identified among wild-type FLT3 AMLs. This pattern was highly enriched in NPM1 and DNMT3A mutants, and particularly in combined NPM1/DNMT3A mutants. CONCLUSIONS: We identified a FLT3 mutation-like gene expression pattern in AML which was highly enriched in NPM1 and DNMT3A mutations. Future analysis about the predictive role of this biomarker among wild-type FLT3 patients treated with FLT3 inhibitors is envisaged.
Authors: Elli Papaemmanuil; Moritz Gerstung; Hartmut Döhner; Peter J Campbell; Lars Bullinger; Verena I Gaidzik; Peter Paschka; Nicola D Roberts; Nicola E Potter; Michael Heuser; Felicitas Thol; Niccolo Bolli; Gunes Gundem; Peter Van Loo; Inigo Martincorena; Peter Ganly; Laura Mudie; Stuart McLaren; Sarah O'Meara; Keiran Raine; David R Jones; Jon W Teague; Adam P Butler; Mel F Greaves; Arnold Ganser; Konstanze Döhner; Richard F Schlenk Journal: N Engl J Med Date: 2016-06-09 Impact factor: 91.245
Authors: Matheus F Bezerra; Aleide S Lima; Maria-Riera Piqué-Borràs; Douglas R Silveira; Juan L Coelho-Silva; Diego A Pereira-Martins; Isabel Weinhäuser; Pedro L Franca-Neto; Lynn Quek; Anna Corby; Mayara M Oliveira; Marinus M Lima; Reijane A de Assis; Paula de Melo Campos; Bruno K Duarte; Israel Bendit; Vanderson Rocha; Eduardo M Rego; Fabiola Traina; Sara T Saad; Eduardo I Beltrão; Marcos A Bezerra; Antonio R Lucena-Araujo Journal: Blood Date: 2020-03-12 Impact factor: 22.113
Authors: Thomas Fischer; Richard M Stone; Daniel J Deangelo; Ilene Galinsky; Elihu Estey; Carlo Lanza; Edward Fox; Gerhard Ehninger; Eric J Feldman; Gary J Schiller; Virginia M Klimek; Stephen D Nimer; D Gary Gilliland; Catherine Dutreix; Alice Huntsman-Labed; Jodi Virkus; Francis J Giles Journal: J Clin Oncol Date: 2010-08-23 Impact factor: 44.544
Authors: G E Nybakken; J Canaani; D Roy; J D Morrissette; C D Watt; N P Shah; C C Smith; A Bagg; M Carroll; A E Perl Journal: Leukemia Date: 2015-11-20 Impact factor: 11.528
Authors: Alexander E Perl; Giovanni Martinelli; Jorge E Cortes; Andreas Neubauer; Ellin Berman; Stefania Paolini; Pau Montesinos; Maria R Baer; Richard A Larson; Celalettin Ustun; Francesco Fabbiano; Harry P Erba; Antonio Di Stasi; Robert Stuart; Rebecca Olin; Margaret Kasner; Fabio Ciceri; Wen-Chien Chou; Nikolai Podoltsev; Christian Recher; Hisayuki Yokoyama; Naoko Hosono; Sung-Soo Yoon; Je-Hwan Lee; Timothy Pardee; Amir T Fathi; Chaofeng Liu; Nahla Hasabou; Xuan Liu; Erkut Bahceci; Mark J Levis Journal: N Engl J Med Date: 2019-10-31 Impact factor: 91.245
Authors: Adrián Mosquera Orgueira; Andrés Peleteiro Raíndo; Miguel Cid López; Beatriz Antelo Rodríguez; José Ángel Díaz Arias; Roi Ferreiro Ferro; Natalia Alonso Vence; Ángeles Bendaña López; Aitor Abuín Blanco; Laura Bao Pérez; Paula Melero Valentín; Marta Sonia González Pérez; Claudio Cerchione; Giovanni Martinelli; Pau Montesinos Fernández; Manuel Mateo Pérez Encinas; José Luis Bello López Journal: PLoS One Date: 2022-09-15 Impact factor: 3.752