Karyotypic abnormalities associated with haemopoietic lineage switching are not linked with mutations to p53.
Leukemic cells can undergo lineage switching to display the phenotypic features of another haemopoietic pathway, as exemplified by B lymphoma and erythroleukemic cell lines generating variants with a monocytic appearance. Unlike the diploid parental lines, the vast majority of myeloid derivative lines examined (12 of 13 lines) were aneuploid. As p53 is involved in the maintenance of chromosomal stability, we investigated the role of p53 in the emergence of abnormal karyotypes in cells which had undergone lineage switching. Single strand conformation polymorphism and sequence analysis of cDNA, together with protein immunoprecipitations, were used to assess the p53 status of parental and variant cell lines. Unexpectedly, four or five monocytic lines with chromosomal alterations contained wild type p53. Conversely, a p53 point mutation found in one aneuploid monocytic line was also present in the diploid parental pre-B cell. These results provide strong evidence that mechanisms other than p53 mutations are responsible for karyotypic abnormalities seen in cells that have undergone lineage switching.
Colley
S M
SM
Department of Biochemistry, University of Western Australia, Royal Perth Hospital, Perth, Australia.
Chappell
D S
DS
Busfield
S J
SJ
Voon
D C
DC
Klinken
S P
SP
D000782:Aneuploidy; D000818:Animals; D019070:Cell Lineage; D002869:Chromosome Aberrations; D004171:Diploidy; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53