Foetal-specific contributors to infant MLL-AF4-driven Acute Lymphoblastic Leukaemia

As MLL-rearranged infant leukaemia is known to initiate in utero, we sought to identify developemntal genes expressed in foetal cells that may aid leukaemogenesis. Bulk RNA-Seq was therefore carried out on mouse and human foetal liver blood progenitors (lymphoid-primed multipotent progenitors [LMPPs] and haematopoietic stem cells/ multipotent progenitor cells [HSC/MPPs]) and compared with the same cell types isolated from developmentally later human cord blood and mouse adult bone marrow. Overall design: For the human samples, HSC/MPPs (CD34+ CD38- CD45RA-) and LMPPs (CD34+ CD38- CD45RA+) were sorted from 13-19 week old foetal livers, and HSC/MPPs from cord blood. For the mouse samples, LMPPs (Lin- Sca1+ ckit+ CD45+ B220- CD19- Flt3+) were sorted from wild-type, VEC-Cre+ controls and Mll-AF4-expressing E14.5 foetal livers and from wild-type 8-10 week. Cell populations were analysed by bulk RNA-Seq old adult bone marrow.