Drivers of secondary-like acute myeloid leukemia: internalizing the external

Acute myeloid leukemia (AML) is a biologically heterogeneous disease which can be broadly classified into 2 disease categories. The first category is marked by swift AML development linked to younger age at diagnosis and better prognosis, the other category represents a developmentally slow AML taking years to evolve and is linked to older age at diagnosis and worse survival, termed secondary-like AML (s-AML-like). The slow disease onset of s-AML-like is indicative that factors extrinsic to the leukemic cells, deriving from proximal non-leukemic cells, play a pivotal role in supporting leukemic outgrowth. Chronic inflammation commonly seen in the old might facilitate this phenomenon. In this project I will study the leukemic and proximal non-leukemic cells to determine whether mechanisms operative within the leukemic cells or extrinsic factors altering leukemic cell behaviour might explain s-AML-like development in the old.