Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia

Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL

Understanding the cancer stem cell

The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at least in some malignancies. Improved experimental models are beginning to uncover a less rigid structure to CSC biology, in which the concepts of functional plasticity and clonal evolution must be incorporated into the traditional models. Slowly the genetic programmes and biological processes underlying stem cell biology are being elucidated, opening the door to the development of drugs targeting the CSC. The aim of ongoing research to understand CSCs is to develop novel stem cell-directed treatments, which will reduce therapy resistance, relapse and the toxicity associated with current, non-selective agents

Modelling soils, lanscapes and waters using the gOcad geomodel: a perspective. Résumé

National audienc

Nosocomial and non-nosocomial Clostridium difficile infections in hospitalised patients in Belgium: compulsory surveillance data from 2008 to 2010.

&lt;p&gt;Surveillance of Clostridium difficile infection (CDI) is compulsory in Belgian hospitals. Our objectives were to compare incidence and case characteristics of nosocomial infections (Nc-CDI) with onset of diarrhoea more than two days after hospital admission, with non-nosocomial cases (Nnc-CDI). The database included inpatients from 2008 to 2010. Of 8,351 cases reported by 150 hospitals, 3,102 (37%) were classified as Nnc-CDI and 5,249 (63%) as Nc-CDI. In 2010, the mean incidence per 1,000 admissions was 0.95 for Nc-CDI and 0.56 for Nnc-CDI. Both incidences were relatively stable over the three years, with a slight decrease in 2010 (p&lt;0.01). Onset of symptoms in Nnc- CDI cases took place in the community (57.1%), nursing homes (14.2%) or hospitals (17.5%); data for 11.2%were missing. Nnc-CDI cases were younger than Nc-CDI (median age 75 vs. 79 years, p&lt;0.001), and more likely to be women (62% vs. 57%, p&lt;0.001) and to have pseudomembranous colitis (5.3% vs. 1.6%, p&lt;0.001). In 2009, C. difficile ribotype 027 was found in 32 of 70 reporting hospitals compared with 19 of 69 in 2010 (p&lt;0.03). Although our study population only included hospitalised patients, the results do not support the hypothesis of an increase in the incidence of severe community-associated CDI.&lt;/p&gt;</p