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The highly utilized KC model has a reported lethality rate of about 30%, which has been attributed to pancreas cancer. However, a competing cause of lethality in KC mice is due to the activation of mutant- Kras  gene ( Kras G12D/+) in the multipotent progenitor cells (MPP), and subsequent development of  Kras -mutant T-cell acute lymphoblastic leukemia (T-ALL). Overall, 20% (5/25) of KC mice developed T-ALL by 9 months of age. Transplantation of pooled bone marrow from KC mice into CD45 congenic mice caused T-ALL in 100% of recipient mice, confirming that mutant- Kras  expression in the hematologic compartment is driving the development of T-ALL in the KC mouse model. These results are an essential consideration for investigators using this model. Further, the lower penetrance of T-ALL in KC mice (versus existing leukemia models) suggests this model could be considered as an alternative research model to evaluate onset and factors that exacerbate the development of T-ALL.

Pdx1 expression in hematopoietic cells activates Kras -mutation to drive leukemia in KC ( Pdx1-Cre; LSL-Kras G12D/+ ) mice