Dr
Marc Ansari

Role of the Fanconi anaemia pathway genes in determining clinical response to myeloablative conditioning regimen with busulfan and cyclophosphamide in children receiving a hematopoietic stem cell transplantation

Bone marrow transplants are always preceded by a preparatory treatment known as conditioning, which aims to destroy as many cancer cells as possible. The most common conditioning treatment in paediatric oncology consists of a combination of busulfan and cyclophosphamide. These two molecules work mainly by interfering with the DNA of cancer cells, inducing them to die by apoptosis. However, outcomes vary greatly from patient to patient. One possible explanation is that cancer cells, like all cells, contain “repair tools” capable of repairing DNA damaged by busulfan and cyclophosphamide. The researchers’ hypothesis is that some of these “repair tools” are expressed differently from patient to patient, and that these differences may explain the variation in their prognosis. In brief, the existence of “strong repair tools” may help cancer cells defend themselves, resulting in a more negative prognosis for the patient.

Using a group of 200 patients provided by the EBMT (European Society for Blood and Marrow Transplantation), Dr Ansari and his team propose to analyse the polymorphism of certain repair tools (BRCA1, RAD51, ATM and FANCD2). This innovative exploratory project builds on the lead researcher’s expertise in biology and can be fully carried out by this research group at the Geneva University Hospitals. The hope is that it will lead to a prospective evaluation of the above parameters in the context of a wider study.

Prof.
Thomas Lecompte

Proteomic study of Philadelphia-negative myeloproliferative neoplasia (Bcr-Abl)

Primitive polycythemia, essential thrombocytopenia and myelofibrosis are all classified as BCR-ABL negative myeloproliferative neoplasias (chronic leukaemias). The complications associated with these cancers, namely haemorrhage and arterial or venous thrombosis, seriously impact patients’ quality of life and can pose an obstacle to treatment. Yet their physiopathology is still poorly understood.
In this project, Prof. Lecompte and Dr Sanchez aim to identify the proteins causing the platelet dysfunction that leads to thrombosis or haemorrhage by analysing the patients’ proteic components (the proteome of their platelets).

Prof.
Marguerite Neerman-Arbez

Role of micro-RNAs in the post-transcriptional regulation of fibrinogen gene expression

Fibrinogen, a precursor of fibrin, plays a central role in the formation of blood clots. It is synthesised in the liver by cells called “hepatocytes”. The amount of fibrogen present in the blood varies from person to person; it is currently considered an important risk factor for cardiovascular disease. For several years, Prof. Neerman-Arbez and her team have been investigating the regulation mechanisms of fibrogen.
In previous research supported by the Foundation (two articles published in Blood in 2010 and 2011), the team showed that certain microRNAs (especially microRNA-29) play an important role in the expression of the relevant genes. The goal of this project is to determine the mechanisms by which these molecules influence the regulation of fibrinogen. Preliminary results indicate that microRNAs do not act directly on the regulation of fibrinogen gene expression but instead on one or more targets at the intermediate level.

Prof.
Olivier Spertini

Role of selectin ligands in leukemia cell adhesion and proliferation

For several years, Prof. Spertini has been researching ways in which the behaviour of leukaemias is influenced by their microenvironment. As in other cancers, leukaemic cells cohabitate alongside normal cells, which they try to exploit as a source of nutrients. This combination of cells is called a tumour microenvironment. It seems likely that selectins, a group of molecules expressed by endothelial cells, platelets and immune cells, which mediate interactions between normal and leukaemic cells, play an important role in this process. In this project, Prof. Spertini proposes to investigate the intra-cellular consequences of selectin interactions (on normal cells) and their ligands (expressed by leukaemic cells). This research will help determine the importance of those interactions in cell proliferation, differentiation and migration.