Alterations of p53 and Rb genes in a novel human GM-CSF-dependent myeloid cell line (OHN-GM) established from therapy-related leukaemia.
A novel GM-CSF-dependent myeloid cell line, OHN-GM, was established from a patient who developed acute myelogenous leukaemia (AML) as a consequence of myelodysplastic syndrome (MDS). As the patient had previously received cytotoxic chemotherapy for Hodgkin's disease, the MDS and AML were probably related to such therapy. Sequential karyotypic analysis established a del(5q) as the initial cytogenetic abnormality. Additional alterations, including t(10;13)(q24;q14), had developed subsequently during disease progression. Southern blot analysis of OHN-GM cells suggested deletion of one allele of the IRF-1 gene, although no aberrant transcripts were detected. Fluorescence in situ hybridization analysis revealed the deletion of the Rb gene due to the t(10;13)(q24;q14) translocation, and Western blot analysis demonstrated the absence of Rb protein in OHN-GM cells. Finally, the OHN-GM cells exhibited two missense point mutations in highly conserved regions of the p53 gene. These observations suggest that a multistep process, involving alterations of Rb and p53 genes, may have contributed to the patient's disease development and progression. To our knowledge, OHN-GM is the first cell line derived from a therapy-related AML. These cells may aid the investigation of leukaemogenesis as well as the biology of secondary leukaemia.
Nagai
M
M
First Department of Internal Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan.
Fujita
M
M
Ikeda
T
T
Ohmori
M
M
Kuwabara
H
H
Yamaoka
G
G
Tanaka
K
K
Kamada
N
N
Taniwaki
M
M
Inoue
T
T
Irino
S
S
Takahara
J
J
D000954:Antigens, Surface / Q000032:analysis; D015139:Blotting, Southern; D015153:Blotting, Western; D002879:Chromosomes, Human, Pair 10; D002882:Chromosomes, Human, Pair 13; D016161:Genes, Retinoblastoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy; D017354:Point Mutation; D017421:Sequence Analysis; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface