CSF1R as a marker of lineage plasticity in MLL-AF9 infant leukaemia

MLL-AF9 translocations can cause either AML or B-ALL in infants. The haematopoietic progenitor cell in which this choice occurs and the underlying mechanisms are still unknown. Given the reported existence of foetal haematopoietic precursors (LMPPs), characterised by CSF1R expression, that possess dual B-myeloid potential, we sorted CSF1R+ and CSF1R- LMPPs following MLL-AF9 induction to test whether CSF1R influences the lineage choice in the context of MLL-AF9 expression. Our data show that MLL-AF9+CSF1R+ LMPPs are more proliferative and have higher plasticity than CSF1R- cells, and induce a faster disease progression, when injected into NSG recipients. Importantly, only CSF1R+ cells from primary recipients fully engrafted secondary and tertiary recipients, which showed myeloblast infiltration in spleen, liver and peripheral blood. Surprisingly, in one of our recipients we saw for the first-time a mixed phenotype and potential lineage switching, confirming higher plasticity of CSF1R+ cells. RNA-seq analysis of MLL-AF9+ CSF1R+/- LMPPs is ongoing to define transcriptional differences, and to find and validate gene candidates driving lineage plasticity in MLL-AF9+ CSF1R+LMPPs.

Publication History

Article published online:
12 May 2023