Identification de biomarqueurs de réponse à l'azacitidine dans les leucémies aigues myéloïdes du sujet âgé

Abstract : Elderly patients with acute myeloid leukemias (AML) represent the most frequent acute leukemias. Although they differ in their pathophysiology, they all share an adverse prognosis. Azacitidine has become one of the reference low-intensity frontline therapy for patients deemed unfit for intensive chemotherapy. Patients selection between these 2 options remains controversial. Predictive biomarkers of response to azacitidine should allowed to rationalize this decision making. Classical prognosis factors of a cohort of 334 newly diagnosed AML lack of precision to determine the optimum strategy for any individual patient. By sequencing of a 224-patients series of azacitidine-treated AML patients, we demonstrate an adverse impact of TP53 mutation on overall survival, irrespective of the functional characterization of p53 mutants. Exome sequencing of 49 patients with extreme phenotype as defined by their response under azacitidine (26 responders versus 23 non-responders), followed by targeted sequencing of 4 common polymorphisms in a validation set of 175 patients, showed a positif impact of MECOM rs7622799 on overall survival.
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Pierre Bories. Identification de biomarqueurs de réponse à l'azacitidine dans les leucémies aigues myéloïdes du sujet âgé. Cancer. Université de Strasbourg, 2018. Français. ⟨NNT : 2018STRAJ086⟩. ⟨tel-02289668⟩

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