Generation of human acute lymphoblastic leukemia xenografts for use in oncology drug discovery

Curr Protoc Pharmacol. 2015 Mar 2:68:14.32.1-14.32.19. doi: 10.1002/0471141755.ph1432s68.

Abstract

The establishment of reproducible mouse models of acute lymphoblastic leukemia (ALL) is necessary to provide in vivo therapeutic test systems that recapitulate human ALL, and for amplification of limited amounts of primary tumor material. A popular assay is the primary xenograft model that utilizes immunocompromised mice. The protocol includes injection of primary patient tumor specimens into mice with subsequent serial passaging of the tumors by retransplants of cells harvested from the mouse bone marrow and spleen. The tumors generated are then used for genomic profiling, ex vivo compound testing, mechanistic studies and retransplantation. Detailed in this unit are procedures for the establishment and maintenance of primary ALL xenograft panels for use in basic research and translational studies.

Keywords: acute lymphoblastic leukemia; mouse model; xenograft.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19
  • Bone Marrow Cells / chemistry
  • Cell Culture Techniques / methods
  • Cell Line, Tumor / transplantation
  • Cell Separation / methods
  • Centrifugation, Density Gradient / methods
  • Coloring Agents
  • Disease Models, Animal
  • Drug Discovery
  • Erythrocytes / chemistry
  • Female
  • Flow Cytometry
  • Graft Survival
  • Heterografts / growth & development*
  • Humans
  • Indicators and Reagents
  • Leukocytes, Mononuclear / chemistry
  • Male
  • Mice, Inbred NOD
  • Microspheres
  • Neoplasm Transplantation / methods*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  • Spleen / chemistry
  • Spleen / cytology
  • Tissue Culture Techniques / methods*

Substances

  • Antigens, CD19
  • Coloring Agents
  • Indicators and Reagents