BCL2L10 is a predictive factor for resistance to Azacitidine in MDS and AML patients

Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment. These patients have a drastically reduced life expectancy as compared to sensitive patients. Therefore identifying predictive factors for AZA resistance is of great interest to propose alternative therapeutic strategies for non-responsive patients. We generated AZA-resistant myeloid cell line (SKM1-R) that exhibited increased expression of BCL2L10 an anti-apoptotic Bcl-2 family member. Importantly, BCL2L10 knockdown sensitized SKM1-R cells to AZA effect suggesting that increased BCL2L10 expression is linked to AZA resistance in SKM1-R. We next established in 77 MDS patients that resistance to AZA is significantly correlated with the percentage of MDS or AML cells expressing BCL2L10. In addition, we showed that the proportion of BCL2L10 positive bone marrow cells can predict overall survival in MDS or AML patients. We propose a convenient assay in which the percentage of BCL2L10 expressing cells as assessed by flow cytometry is predictive of whether or not a patient will become resistant to AZA. Therefore, systematic determination of BCL2L10 expression could be of great interest in newly diagnosed and AZA-treated MDS patients

Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC).

International audienceBACKGROUND AND OBJECTIVES: High-dose chemotherapy with allogeneic stem cell transplantation (SCT) has proven to be a successful treatment for low-grade lymphoma (LGL), but is associated with considerable transplant-related mortality (TRM). In an effort to reduce toxic mortality while maintaining the graft-versus-leukemia effect, allogeneic SCT has been combined with a reduced-intensity conditioning (RIC) regimen. The aim of this study was to determine the outcome of patients with LGL treated with RIC allogeneic SCT. DESIGN AND METHODS: This retrospective multicenter study included 73 patients with relapsed or refractory LGL allografted after a RIC regimen between 1998 and 2005 whose data were recorded in a French registry. RESULTS: Patients received a median of three lines of therapy prior to RIC allogeneic SCT. The most widely used conditioning regimens were fludarabine + busulfan + antithymocyte globulin (n=43) and fludarabine + total body irradiation (n=21). Prior to allografting, patients were in complete response (CR; n=21), partial response (PR; n=33) or had chemoresistant disease (n=19). The median follow-up was 37 months (range, 16 to 77 months). In patients in CR, PR and chemoresistant disease, the 3-year overall survival rates were 66%, 64% and 32%, respectively, while the 3-year event-free survival rates were 66%, 52% and 32%, respectively. The 3-year cumulative incidences of TRM were 32%, 28% and 63%, respectively. The incidence of relapse was 9.6%. INTERPRETATION AND CONCLUSIONS: Although associated with significant TRM, RIC allogeneic SCT in advanced chemosensitive disease leads to long-term survival

Male Microchimerism at High Levels in Peripheral Blood Mononuclear Cells from Women with End Stage Renal Disease before Kidney Transplantation

Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

La renaissance du nucléaire italien

Dans un contexte de recherche de compétitivité économique, la double nécessité de décroissance, d’une part de la forte dépendance énergétique du pays et, d’autre part, des rejets d’oxydes de carbone tels que programmés par la Commission Européenne, impose à l’Italie de gagner le double défi de la relance de l’énergie nucléaire et également du développement accru des énergies renouvelables. Pour gagner ces deux défis, le gouvernement italien, s’il doit rechercher au plan politique une approche plus bipartisane doit, surtout, vaincre la réticence des populations en particulier dans les régions directement concernées et ce, au prix de grands efforts de concertation et de communication mettant en jeu l’ensemble des parties prenantes. Dans ce contexte, le partage du retour d’expérience de l’Italie avec les pays qui ont réussi leur programme nucléaire et notamment avec la France, apparaît comme indispensable

Adsorption, désorption et atomisation de l'oxygène sur le platine

Nous avons étudié les réactions d'adsorption, de désorption et d'atomisation de l'oxygène sur le platine. Le rendement de choc d'adsorption a pour valeur 0,14. Il correspond à un seul état dissociatif apparent à 25 °C et décroît lorsque la quantité adsorbée atteint 1,50.1014 atomes/cm2. A saturation, la couche adsorbée correspond à la formule Pt2O. Le rendement de choc d'atomisation a pour valeur 0,12 dans la zone de faible pression. L'adsorption n'est donc pas activée. L'énergie d'activation de désorption sous forme moléculaire suit la loi :E(n) = 58 000 — 2,310-11 navec n, nombre d'atomes adsorbés.Les valeurs des facteurs de fréquence des vitesses de désorption et d'atomisation sont en faveur de la formation d'un complexe d'adsorption beaucoup plus mobile que les atomes adsorbés

Le blastocyste en milieu séquentiel (avantages et inconvénients)

PARIS-BIUP (751062107) / SudocSudocFranceF

Application de la spectrométrie d’électrons Auger au système platine-oxygène à haute température

Par desorption éclair nous montrons que le taux de recouvrement de la surface en oxygène θ est proportionnel à la hauteur pic à pic du signal Auger de ce gaz.Cette calibration permet de tracer des isostères (dans la gamme 0,15 < θ < 0,4) dont la pente conduit à la détermination de la chaleur d’adsorption 52 ± 5 kcal à faible degré de recouvrement, 42 ± 5 kcal à fort degré de recouvrement