Mutant type glutathione S-transferase theta 1 gene homologue to mTOR in myelodysplastic syndrome: possible clinical application of rapamycin

Leuk Lymphoma. 2003 Jul;44(7):1179-85. doi: 10.1080/1042819031000077052.

Abstract

In this study, we observed the expression of the GSTT-1 gene in patients with myelodysplastic syndrome (MDS) at the messenger RNA level. Reverse transcription-polymerase chain reaction (RT-PCR) for GSTT-1 was performed with a pair of primers complementary to the 5' coding section and the 3' coding section of the GSTT-1 cDNA for amplifying the 623-bp band. Among 20 patients with MDS, 8 patients showed the expected 623-bp band on RT-PCR, and 12 patients showed a 500-bp band on RT-PCR, indicating that a 123-bp sequence was deleted as a mutant of the GSTT-1 gene. Furthermore, a BLAST DNA search showed that the deletion of a 123 bp sequence creates a sequence that is 63% homologous to human FKBP-rapamycin associated protein (FRAP); this protein has been termed a mammalian target of rapamycin (mTOR). We respectively transfected the wild type and the mutant type GSTT-1 gene in an expression vector to two cell lines (K562 and HL-60). The stable transformants for the wild type and the mutant type GSTT-1 genes were made by G418 selection. Interestingly, rapamycin could induce significant growth inhibition of the stable transformants for mutant type GSTT-1, which was indicative of apoptosis, but not that of those for wild type GSTT-1. These results suggest that rapamycin could be included in the therapeutic modality for the patients with MDS who have the mTOR sequences in GSTT-1 gene.

Publication types

  • Comparative Study

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects
  • Base Sequence
  • Cell Division / drug effects
  • DNA Primers
  • Gene Deletion
  • Glutathione Transferase / genetics*
  • HL-60 Cells
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • K562 Cells
  • Molecular Sequence Data
  • Mutation / genetics
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / enzymology*
  • Protein Kinases / genetics*
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sirolimus / therapeutic use*
  • TOR Serine-Threonine Kinases
  • Tacrolimus Binding Proteins / metabolism
  • Transfection

Substances

  • Annexin A5
  • DNA Primers
  • Immunosuppressive Agents
  • RNA, Messenger
  • RNA, Neoplasm
  • glutathione S-transferase T1
  • Glutathione Transferase
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Tacrolimus Binding Proteins
  • Sirolimus