NOD/SCID IL2Rγ-null mouse xenograft model of human p53-mutated chronic lymphocytic leukemia and ATM-mutated mantle cell lymphoma using permanent cell lines

Leuk Lymphoma. 2015;56(11):3198-206. doi: 10.3109/10428194.2015.1034701. Epub 2015 May 12.

Abstract

Xenograft models represent a promising tool to study the pathogenesis of hematological malignancies. To establish a reliable and appropriate in vivo model of aggressive human B-cell leukemia and lymphoma we xenotransplanted four p53-mutated cell lines and one ATM-mutated cell line into immunodeficient NOD/SCID IL2Rγ-null mice. The cell lines MEC-1, SU-DHL-4, JEKO-1, REC-1, and GRANTA-519 were transplanted intraperitoneally or subcutaneously and the engraftment was investigated using immunohistochemistry and flow cytometry. We found significant differences in engraftment efficiency. MEC-1, JEKO-1 and GRANTA-519 cell lines engrafted most efficiently, while SU-DHL-4 cells did not engraft at all. MEC-1 and GRANTA-519 massively infiltrated organs and the whole intraperitoneal cavity showing very aggressive growth. In addition, GRANTA-519 cells massively migrated to the bone marrow regardless of the transplantation route. The MEC-1 and GRANTA-519 cells can be especially recommended for in vivo study of p53-mutated chronic lymphocytic leukemia and ATM-mutated mantle cell lymphoma, respectively.

Keywords: Chronic lymphocytic leukemia; NSG mouse; mantle cell lymphoma; xenograft model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Biomarkers
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Gene Knockout Techniques
  • Heterografts
  • Humans
  • Interleukin Receptor Common gamma Subunit / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / pathology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Mutation*
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Biomarkers
  • Interleukin Receptor Common gamma Subunit
  • Tumor Suppressor Protein p53
  • Ataxia Telangiectasia Mutated Proteins