Pdx1 expression in hematopoietic cells activates Kras-mutation to drive leukemia in KC (Pdx1-Cre; LSL-KrasG12D/+ ) mice

• Published in: Leukemia & lymphoma 2023-05, Vol.64 (6), p.1112-1122
• Main Authors: Walcheck, Morgan T., Nukaya, Manabu, Ranheim, Erik A., Matkowskyj, Kristina A., Ronnekleiv-Kelly, Sean
• Format: Article
• Language: English
• Subjects: Animals; hematopoietic; KC mice; Kras; Mice; Mice, Transgenic; Mutation; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pdx1; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; T-ALL; T-cell acute lymphoblastic leukemia
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2023.2202788

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.