Alterations of p53 and Rb genes in a novel human GM-CSF-dependent myeloid cell line (OHN-GM) established from therapy-related leukaemia

Br J Haematol. 1997 Aug;98(2):392-8. doi: 10.1046/j.1365-2141.1997.2413058.x.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / analysis
  • Blotting, Southern
  • Blotting, Western
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 13
  • Genes, Retinoblastoma / genetics*
  • Genes, p53 / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Myeloid, Acute / chemically induced
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Point Mutation
  • Sequence Analysis
  • Translocation, Genetic
  • Tumor Cells, Cultured

Substances

  • Antigens, Surface