85 research outputs found

    Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias

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    <p>Abstract</p> <p>Background</p> <p>Gene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.</p> <p>Methods</p> <p>We searched for mutations in the <it>ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 </it>and <it>WT1 </it>genes in 65 myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without balanced translocation or complex karyotype.</p> <p>Results</p> <p>Mutations in <it>ASXL1 </it>and <it>CBL </it>were frequent in refractory anemia with excess of blasts. Mutations in <it>TET2 </it>occurred with similar frequency in MDSs and AMLs and associated equally with either <it>ASXL1 </it>or <it>NPM1 </it>mutations. Mutations of <it>RUNX1 </it>were mutually exclusive with <it>TET2 </it>and combined with <it>ASXL1 </it>but not with <it>NPM1</it>. Mutations in <it>FLT3 (</it>mutation and internal tandem duplication), <it>IDH1</it>, <it>IDH2</it>, <it>NPM1 </it>and <it>WT1 </it>occurred primarily in AMLs.</p> <p>Conclusion</p> <p>Only 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.</p

    Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases

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    The ASXL1 gene is one of the most frequently mutated genes in malignant myeloid diseases. The ASXL1 protein belongs to protein complexes involved in the epigenetic regulation of gene expression. ASXL1 mutations are found in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment

    Revolutionary spirit preceding the French revolution.

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    Identification of new molecular targets in myelodysplastic syndromes and acute myeloid leukemias

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    Au sein des hémopathies myéloïdes malignes, les syndromes myélodysplasiques(SMD) et les leucémies aiguës myéloïdes (LAM) représentent des pathologies complexes ethétérogènes résultant d’anomalies clonales des cellules souches médullaires. Elles sontcaractérisées par une hématopoïèse inefficace provoquant des cytopénies sanguines graves.Les connaissances sur les anomalies moléculaires des SMD et des LAM, notammentà caryotype normal, sont globalement pauvres et leur physiopathologie encore mal connue.Une meilleure définition moléculaire est nécessaire pour une évaluation pronostique plusprécise de ces hémopathies et pour optimiser secondairement les stratégies thérapeutiques.Cette thèse présente un panorama des classifications cytogénétiques et moléculairesactuelles des SMD et LAM ainsi que l’étude de certaines altérations moléculairesrencontrées dans ces maladies.Grâce à l’apport des techniques d’analyse génomique à grande échelle, notamment laCGH-array, notre laboratoire a identifié de nouvelles altérations génétiques, parmi lesquellesles mutations du gène ASXL1, ainsi que des altérations des gènes codant les protéines de laCohésine et des régulateurs de la protéine CBL. Nous avons analysé une combinaison demutations de gène et émis l’hypothèse d’un modèle de leucémogenèse à 4 classes demutations, afin d’apporter des pistes dans la compréhension de la physiopathologie des SMDet LAM.Among myeloid malignancies, myelodysplastic syndromes (MDSs) represent a groupof complex diseases characterized by clonal abnormalities of bone marrow hematopoieticprecursor cells. They are defined by an ineffective hematopoiesis leading to peripheralcytopenias. About 40% of MDSs secondarily evolve to acute myeloid leukemia (AML).This risk of transformation is evaluated by several international prognostic scoringsystems like IPSS and WPSS. The WHO classification recognizes several classes of MDSsessentially based on morphology and cytogenetics features, some with a high progressionrisk, like refractory anemia with excess of blasts type 2, others with a low risk, likerefractory anemia with ringed sideroblasts. However, the classification of MDSs is stillunsatisfactory and relevant prognostic markers allowing earlier treatments for patients with ahigh risk of transformation are still lacking. The physiopathology of SMDs and AMLs withnormal karyotype remains unclear. Currently, the only potentially curative treatment isallogenic stem cell transplant, which is feasible for a restricted number of patients and candisplay side effects and failures.A better knowledge of the molecular biology of MDSs and AMLs is necessary for abetter understanding of these diseases and may provide new early prognosis indicators andbetter strategies of treatments

    Manuscrit en langue d'oc trouvé à Cordes

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    Rocquain Félix. Manuscrit en langue d'oc trouvé à Cordes. In: Comptes rendus des séances de l'Académie des Inscriptions et Belles-Lettres, 24ᵉ année, N. 3, 1880. pp. 223-224

    La cour de Rome et l'esprit de réforme avant Luther

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    Marca de ed. en portContiene : t. I. La théocratie, apogée du pouvoir pontifical -- t. II. Les abus, décadence de la papauté -- t. III. Le grand schisme, les approches de la Réform

    La cour de Rome et l'esprit de réforme avant Luther

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    Marca de ed. en portContiene : t. I. La théocratie, apogée du pouvoir pontifical -- t. II. Les abus, décadence de la papauté -- t. III. Le grand schisme, les approches de la Réform

    Les archives de l'Hôtel-Dieu de Pontoise.

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    Rocquain de Courtemblay Félix. Les archives de l'Hôtel-Dieu de Pontoise.. In: Bibliothèque de l'école des chartes. 1861, tome 22. pp. 505-517
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