Positron emission tomography imaging analysis of G2A as a negative modifier of lymphoid leukemogenesis initiated by the BCR-ABL oncogene.
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.
Le
Lu Q
LQ
Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, CA 90095, USA.
Kabarowski
Janusz H S
JH
Wong
Stephane
S
Nguyen
Khoi
K
Gambhir
Sanjiv S
SS
Witte
Owen N
ON
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers / Q000737:chemistry; D016044:Fusion Proteins, bcr-abl / Q000502:physiology*; D018259:Herpesvirus 1, Human; D006801:Humans; D007942:Leukemia, Experimental / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics*; D012313:RNA / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014055:Tomography, Emission-Computed
D018797:Cell Cycle Proteins; D017931:DNA Primers; C115270:G2A receptor; D015513:Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D012313:RNA; D013937:Thymidine Kinase; D016044:Fusion Proteins, bcr-abl