stem cells

Dominique Bonnet : Cross-talk between LSCs and their microenvironment

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It has become clear both in solid tumours and in leukaemia that cancer stem cells depend on their microenvironment to grow and expand.

In AML, we know that LSCs cannot be maintained ex vivo without the addition of a stroma support, indicating that LSCs are dependent on their microenvironment for their survival/maintenance. Understanding the crosstalk between LSCs and their microenvironment is thus crucial to better understand this dependency and potentially use this to target LSC in vivo.

We thus started a project trying to better define the factors involved in this crosstalk. AML samples were co-cultured ex vivo with Mesenchymal Stroma Cells (MSC), and after one week micro-array analysis was performed on sorted stroma cells. Using pathway analysis and the Gene Go program, we built a network of the combined datasets.

Further studies will be undertaken to evaluate the effect of the different keys factors. If any of these factors affect the growth/differentiation/apoptosis of AML, we will further investigate one/more pathway(s) in more detail in vitro but also in vivo using knock-down approaches.