CHARACTERIZATION OF THE METABOLIC AND EPIGENETIC DETERMINANTS OF SECONDARY ORGAN INFILTRATION IN ACUTE MYELOID LEUKAEMIA

Acute Myeloid Leukaemia (AML) is the most frequent acute leukaemia in adulthood. It is caused by impaired differentiation and clonal expansion of myeloid hematopoietic precursors in the bone marrow, triggering haematopoietic deficiency. It is known that one of the main contributing factors to cancer lethality is its ability to advance beyond its primary infiltration site and disseminate throughout the body. Unfortunately, unlike most solid tumours, leukemic cells uniquely possess the innate ability for migration, making AML a cancer which does not require a high somatic mutation burden to acquire dissemination treats and anchorage-independent growth. Preliminary studies showed a non-random pattern of spreading of leukemic cells, highlighting significant changes in both cell metabolism and epigenome once they reach the secondary site. This suggests that cancer cells crosstalk with their micro-environment generating biological features in these cells which promote tumour progression toward that specific site. Here, we present an effective combination of ChIP-seq, RNA-seq and shRNA- screening to search for some organ-specific signatures which could be responsible for infiltration progression. Employing a niche-specific AML mouse model, we have investigated four secondary infiltration sites therefore characterising metabolic and epigenetic determinants which could explain the causal determinism behind the secondary organ infiltration in AML.