Functional evidence from microcell-mediated chromosome transfer of myeloid leukemia suppressor genes on human chromosomes 7 and 11.
The long arm of human chromosome 7 between 7q22 and 7q36 has been identified as a region harboring one or more tumor-suppressor genes (TSGs) inactivated in acute myeloid leukemia (AML). Additional TSGs mapping to other chromosomes may well be involved in the etiology of this disease. For example, experiments using a mouse model system have indicated the possible presence of an AML TSG at 11p11-12. Microcell-mediated chromosome transfer (MMCT) has been used to introduce human chromosomes 7 and 11 into a murine myeloid leukemia cell line. A proportion of MMCT hybrid clones containing either whole chromosome 7 or fragments of chromosome 11 showed a significant delay in leukemogenic onset when injected into syngeneic mice. Screening of hybrid clones did not associate any human microsatellite markers with decreased leukemogenic potential in vivo. However, preliminary evidence was obtained of allelic loss at chromosomal regions homologous with human 7q22 in murine F1 hybrid AMLs. Our data provide functional evidence of AML-associated TSGs localized to human chromosomes 7 and 11 in support of previously published studies on cytogenetic and allelic losses associated with AML development.
Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire OX11 0RQ, UK.
Jennifer
J
Wilding
Emmy
E
Meijne
Jackie
J
Haines
John
J
Moody
Alan
A
Edwards
Robert F
RF
Newbold
Chris
C
Parris
Roger
R
Cox
Andrew
A
Silver
D000208:Acute Disease; D000818:Animals; D002678:Chimera / Q000235:genetics; D002871:Chromosome Banding; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D002999:Clone Cells; D020732:Cytogenetic Analysis / Q000379:methods; D003598:Cytoskeletal Proteins; D005434:Flow Cytometry / Q000379:methods; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation / Q000379:methods; D021141:Nucleic Acid Amplification Techniques; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D003598:Cytoskeletal Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C429688:TES protein, human; D025521:Tumor Suppressor Proteins; D009195:Peroxidase