Functional evidence from microcell‐mediated chromosome transfer of myeloid leukemia suppressor genes on human chromosomes 7 and 11

Abstract

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.

The manipulation of chromosomes by mankind: the uses of microcell-mediated chromosome transfer

“…Scale bar=5 μm contain genomic regions that suppress nasopharyngeal carcinoma (Cheng et al 2003(Cheng et al , 2004. Chromosome 7 regions (7q22, 7q36) are important in suppressing the neoplastic phenotype of acute myeloid leukaemic cells (Wilding et al 2002). Chromosome 1 carries a region that suppresses tumourigenicity in neuroblastoma (1p) (Bader et al 1991;Oshimura et al 1989).…”

Mechanistic and genetic studies of radiation tumorigenesis in the mouse - implications for low dose risk estimation

“…No LOH other that on chr2 was detected by low density whole genome microsatellite scans (six markers/chromosome) of a limited number of AMLs (Saran et al, unpublished observations). A targeted scan of four regions on chromosomes 5, 6 and 12 (holomologous to human 7q) detected only five LOH events, all in the chr5 region in 23 tumours [27]. Similar targeted high density scans of some 20 or more regions have also failed to detect any significant LOH in radiation-induced AMLs (Silver et al, unpublished observations).…”

Microsatellite instability in radiation-induced murine tumours; influence of tumour type and radiation quality

“…AML cell lines were obtained from primary AML tumours and screened with mono-nucleotide and nine genome-wide di-nucleotide markers. The cell lines screened were Sa2-Jmb1, Mlp3, 3124r12, 7926, 8016, and 8709 (Pazzaglia et al 2000, Wilding et al 2002. .…”