Tools to detect, track and target cancer cells in vivo
Some embodiments include a genetically engineered cell comprising a nucleic acid encoding a detectable polypeptide operably linked to the Msi1 or Msi2 promoter and genetically engineered organisms comprising these genetically engineered cells.
1. An isolated, genetically engineered cell comprising a nucleic acid encoding a detectable polypeptide inserted into an exon of an endogenous Msi1 or Msi2 gene such that said detectable polypeptide is expressed in a form which allows it to be detected.
2. The genetically engineered cell of claim 1 , wherein said cell further comprises one or more transgenes encoding one or more oncogenic polypeptides integrated into the genome, whereby said oncogenic polypeptides encoded by said transgenes are expressed.
3. The genetically engineered cell of claim 2 , wherein said one or more oncogenic polypeptides are associated with adenocarcinoma, pancreatic cancer or leukemia.
4. The genetically engineered cell of claim 2 , wherein said one or more oncogenic polypeptides is selected from the group consisting of Kras polypeptide, BCR-ABL polypeptide, and/or Nup98-HoxA9 transactivator polypeptide.
5. The genetically engineered cell of claim 1 , wherein said cell further comprises a KRASG12D allele.
6. The genetically engineered cell of claim 4 , wherein the oncogenic polypeptide is Kras polypeptide, and wherein the transgene encoding the Kras polypeptide is under the control of a Ptf1a promoter.
7. The genetically engineered cell of claim 1 , wherein said cell further comprises a genetic modification which reduces the level or activity of or inactivates one or more tumor suppressor proteins.
8. The genetically engineered cell of claim 7 , wherein said one or more tumor suppressor protein is selected from the group consisting of p53, p16/INK4A, and SMAD4.
9. The genetically engineered cell of claim 7 , wherein said tumor suppressor is encoded by a nucleic acid which can be conditionally deleted.
10. The genetically engineered cell of claim 1 , wherein the detectable polypeptide comprises a fluorescent polypeptide.
11. The genetically engineered cell of claim 10 , wherein said fluorescent polypeptide comprises eYFP or eGFP.
12. The genetically engineered cell of claim 1 , wherein said cell is capable of forming a tumor.
13. The genetically engineered cell of claim 1 , wherein said cell is a tumor stem cell.
14. The genetically engineered cell of claim 1 , wherein the genetically engineered cell is a precursor T cell.
15. The genetically engineered cell of claim 14 , wherein the precursor T cell is hematopoietic stem cell.