Spatial diversity of abundant and equipotent founder clones in acute lymphoblastic leukaemia

Introduction: In recent years there has been increasing focus on the extent to which intra-tumour heterogeneity influences the development and evolution of cancer. Although there is evidence that ALL samples consist of a genetically heterogeneous subclonal architecture, it is unclear how individual clones differ at the functional level.

Methods: We used a cellular barcoding approach to label individual clones with heritable genetic markers and track their contribution to ALL development.

Results: We demonstrate that xenografted ALL samples consist of high numbers of founder clones. These clones have similar functional potential, in terms of their capability to contribute to the disease in multiple sites and over serial transplants in the absence of external selective pressures. We also show that leukaemia can be locally heterogeneous, with different clonal composition in different bones emerging due to stochastic processes. The spleen acts as a filter for the total blood volume so is representative of the full repertoire of engrafting clones.

Conclusion: Our results show that ALL founder clones are abundant and have similar functional potential in the absence of external selective pressures.