Abstract
Although it is firmly established that endogenous immunity can prevent cancer outgrowth, with a range of immunomodulatory strategies reaching clinical use, most studies on the topic have been restricted to solid cancers. This applies in particular to cancer initiation, where model constraints have precluded investigations of immunosurveillance and immunoediting during the multistep progression into acute myeloid leukemia (AML). Here, we used a mouse model where the chimeric transcription factor MLL-ENL can be conditionally activated in vivo as a leukemic "first-hit," which is followed by spontaneous transformation into AML. We observed similar disease kinetics regardless of whether AML developed in WT or immunocompromised hosts, despite more permissive preleukemic environments in the latter. When assessing transformed AML cells from either primary immunocompetent or immunocompromised hosts, AML cells from all sources could be targets of endogenous immunity. Our data argue against immunoediting in response to selective pressure from endogenous immunity as a universal primary transformation event in AML.