Characterization of leukemia progression in the Cbfb-MYH11 knockin mice by single cell RNA sequencing.

A recurrent inversion of chromosome 16 fuses the genes CBFB and MYH11 and the resultant CBFβ-SMMHC fusion protein acts as a driver of the M4Eo subtype of acute myeloid leukemia (AML). This study utilized single cell RNA-sequencing (scRNA-seq) to assess gene expression changes during the disease progression from normal to pre-leukemic to overt leukemia in the conditional Cbfb-MYH11 knock-in mouse model. The study investigated dynamic shifts in cell types as disease progresses, and gene expression differences between normal and diseased cells. The study identified a novel cell population in the pre-leukemic state with expression of genes involved in immune activation. Overall, this study discovered hematopoietic cells first affected by the expression of CBFβ-SMMHC and identified unique signature genes for the pre-leukemic cells that separate them from the normal hematopoietic cellular milieu.