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Alterations of p53 and Rb genes in a novel human GM‐CSF‐dependent myeloid cell line (OHN‐GM) established from therapy‐related leukaemia
Author(s) -
Nagai Masami,
Fujita Mitsuhiro,
Ikeda TakashiI,
Ohmori Minoru,
Kuwabara Hiroko,
Yamaoka Genji,
Tanaka Kimio,
Kamada Nanao,
Taniwaki Masafumi,
Inoue Tokiko,
Irino Shozo,
Takahara Jiro
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.2413058.x
Subject(s) - cancer research , biology , southern blot , chromosomal translocation , fluorescence in situ hybridization , myeloid , gene , microbiology and biotechnology , immunology , genetics , chromosome
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.