Oncotarget

Clinical Research Papers:

Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes

Raynier Devillier _, Véronique Mansat-De Mas, Veronique Gelsi-Boyer, Cecile Demur, Anne Murati, Jill Corre, Thomas Prebet, Sarah Bertoli, Mandy Brecqueville, Christine Arnoulet, Christian Recher, Norbert Vey, Marie-Joelle Mozziconacci, Eric Delabesse and Daniel Birnbaum

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:8388-8396. https://doi.org/10.18632/oncotarget.3460

Metrics: PDF 1305 views  |   HTML 1318 views  |   ?  


Abstract

Raynier Devillier1,2,3, Véronique Mansat-De Mas5,*, Veronique Gelsi-Boyer2,3,4,*, Cecile Demur5,*, Anne Murati3,4,*, Jill Corre5,*, Thomas Prebet1,3, Sarah Bertoli5, Mandy Brecqueville2,3, Christine Arnoulet4, Christian Recher5,6, Norbert Vey1,2,3, Marie-Joelle Mozziconacci3,4, Eric Delabesse5,6 and Daniel Birnbaum3

1 Hematology Department, Institut Paoli Calmettes, Marseille, France

2 Aix-Marseille University, Marseille, France

3 Département d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, UMR1068 Inserm, Marseille, France

4 Biopathology Department, Institut Paoli Calmettes, Marseille, France

5 Hematology Department, Institut Universitaire du Cancer Toulouse–Oncopole, Toulouse, France

6 Toulouse University, Toulouse, France

* These authors contributed equally to this work

Correspondence to:

Raynier Devillier, email:

Keywords: acute myeloid leukemia, myelodysplasia-related changes, mutational status, ASXL1, TP53

Received: September 24, 2014 Accepted: January 20, 2015 Published: February 28, 2015

Abstract

Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 3460