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

Abstract

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.

Keywords:

• T-cell acute lymphoblastic leukemia
• T-ALL
• Kras
• Pdx1
• hematopoietic
• KC mice

Acknowledgements

The authors would like to acknowledge the Experimental Animal Pathology Lab (EAPL) supported by the UWCCC (P30 CA014520) for use of its facilities and services.

Consent for publication

Not applicable

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

The data generated or analyzed during the study are included in the published article (and the supplementary information).

Additional information

Funding

This work was supported by the American Cancer Society (grant number IRG-15-213-51)[SRK] and the University of Wisconsin Institute for Clinical and Translational Research KL2 Award (UL1TR002373 and KL2TR002374) [SRK]. The first author (MW) was supported by the Morgridge Wisconsin Distinguished Graduate Fellowship in Biotechnology and the National Institutes of Health Award Number T32 ES007015. The funding bodies were not involved in the design of the study, data collection, analysis or interpretation of the data.