Gene expression profiling identifies FLT3 mutation-like cases in wild-type FLT3 acute myeloid leukemia.
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ABSTRACT: 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.
SUBMITTER: Mosquera Orgueira A
PROVIDER: S-EPMC7886212 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Gene expression profiling identifies FLT3 mutation-like cases in wild-type FLT3 acute myeloid leukemia.
Mosquera Orgueira Adrián A Peleteiro Raíndo Andrés A Cid López Miguel M Antelo Rodríguez Beatriz B Díaz Arias José Ángel JÁ Ferreiro Ferro Roi R Alonso Vence Natalia N Bendaña López Ángeles Á Abuín Blanco Aitor A Bao Pérez Laura L Melero Valentín Paula P González Pérez Marta Sonia MS Cerchione Claudio C Martinelli Giovanni G Montesinos Fernández Pau P Pérez Encinas Manuel Mateo MM Bello López José Luis JL
PloS one 20210216 2
<h4>Background</h4>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.<h4>Methods</h4>We analyzed 6 different transcriptomic datasets of AML cases. Differential expression between mutated and wild-type FLT3 AMLs was perform ...[more]
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