Positron emission tomography imaging analysis of G2A as a negative modifier of lymphoid leukemogenesis initiated by the BCR-ABL oncogene

Cancer Cell. 2002 May;1(4):381-91. doi: 10.1016/s1535-6108(02)00058-2.

Abstract

G2A is a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity. Using HSV-TK reporter gene directed positron emission tomography (PET), we demonstrate that prior to any indication of the onset of illness, mice transplanted with BCR-ABL transduced G2A-deficient bone marrow harbor expanded populations of leukemic cells compared to recipients of wild-type bone marrow. The target cell type and anatomical locations of leukemia development are indistinguishable in animals transplanted with G2A+/+ or G2A-/- cells. Shorter disease latency in the G2A-deficient background is associated with an increased rate of cellular expansion. PET can be successfully applied to the temporal and spatial analysis of Bcr-Abl driven leukemic progression and should have utility for the study of other leukemias and lymphomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Transformation, Neoplastic
  • DNA Primers / chemistry
  • Fusion Proteins, bcr-abl / physiology*
  • Herpesvirus 1, Human
  • Humans
  • Leukemia, Experimental / diagnostic imaging*
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / metabolism
  • Lymphoma / diagnostic imaging*
  • Lymphoma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Oncogene Proteins / genetics*
  • RNA / metabolism
  • Receptors, G-Protein-Coupled*
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Simplexvirus / enzymology
  • Simplexvirus / genetics
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Tomography, Emission-Computed

Substances

  • Cell Cycle Proteins
  • DNA Primers
  • G2A receptor
  • Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • RNA
  • Thymidine Kinase
  • Fusion Proteins, bcr-abl