Control of Lineage Commitment in Acute Leukaemia

Introduction: Whilst translocations involving MLL (11q23) result in a spectrum of acute leukaemias, MLL/AF4 is specifically associated with B ALL. We describe an ALL to AML lineage switch patient with identical t(4;11) translocations. We have characterised this case in order to study the control of lineage commitment and the haematopoietic origin of the leukaemia. Methods: RNAseq and DNase hypersensitivity analysis showed genomic fingerprinting consistent with a switch from lymphoid to myeloid lineage. Exome and RNA seq identified 13 novel deleterious mutations in the AML, all of which belong to the top 25% expr…