[Evaluation of the quality of long-term anticoagulation therapy with antivitamin-K in atrial fibrillation]. / Évaluation de la qualité de l'anticoagulation au long cours par antivitamine-K dans la fibrillation auriculaire.

AIM: To assess the quality of long-term anticoagulation therapy with antivitamin-K in patients with atrial fibrillation by measuring the TTR and to determine the factors associated with a good TTR. PATIENTS AND METHODS: This is an observational study conducted over a period of three years (from January 2013 until December 2015) in the outpatient clinic of cardiology of Farhat Hached hospital of Sousse, Tunisia. Pre-established individual plugs were used for data collection. The data analysis was performed using the SPSS Software, version 20. RESULTS: Overall, 200 patients were eligible. Half of the patients did not know the risks of AVK and 29.1% were unaware of their interest. The average TTR was 57.3±18.2%. Good control of anticoagulation was obtained in 24.5% of patients. Those with a≥70% were more autonomous, observant, of urban origin, living in Sousse and Kairouan, with good knowledge about AVK and having a small left atrium. The factors associated negatively with TTR were hypertension, diabetes, old AF, hematological diseases, high number of medications taken daily and the presence of mitral insufficiency, mitral valve replacement, a tricuspid insufficiency or a tricuspid plasty. CONCLUSION: The quality of AVK anticoagulation in AF patients is insufficient. Improving this indicator would reduce the morbidity and mortality associated with AVK treatment.

CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes.

The t(10;11)(p13;q14-21) is found in T-ALL and acute myeloid leukemia and fuses CALM (Clathrin-Assembly protein-like Lymphoid-Myeloid leukaemia gene) to AF10. In order to gain insight into the transcriptional consequences of this fusion, microarray-based comparison of CALM-AF10+ vs CALM-AF10- T-ALL was performed. This analysis showed upregulation of HOXA5, HOXA9, HOXA10 and BMI1 in the CALM-AF10+ cases. Microarray results were validated by quantitative RT-PCR on an independent group of T-ALL and compared to mixed lineage leukemia-translocated acute leukemias (MLL-t AL). The overexpression of HOXA genes was associated with overexpression of its cofactor MEIS1 in CALM-AF10+ T-ALL, reaching levels of expression similar to those observed in MLL-t AL. Consequently, CALM-AF10+ T-ALL and MLL-t AL share a specific HOXA overexpression, indicating they activate common oncogenic pathways. In addition, BMI1, located close to AF10 breakpoint, was overexpressed only in CALM-AF10+ T-ALL and not in MLL-t AL. BMI1 controls cellular proliferation through suppression of the tumor suppressors encoded by the CDKN2A locus. This locus, often deleted in T-ALL, was conserved in CALM-AF10+ T-ALL. This suggests that decreased CDKN2A activity, as a result of BMI1 overexpression, contributes to leukemogenesis in CALM-AF10+ T-ALL. We propose to define a HOXA+ leukemia group composed of at least MLL-t, CALM-AF10 and HOXA-t AL, which may benefit from adapted management.