Possible molecular target therapy with rapamycin in MDS

Leuk Lymphoma. 2006 May;47(5):907-11. doi: 10.1080/10428190500467859.

Abstract

The authors previously reported the mRNA expression of Glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp) in MDS patients. The deletion of 123 bp creates a sequence that is homologues to mammalian target of rapamycin (mTOR). To analyse the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of wild and mutant type GSTT-1 gene of those stable transformants and bone marrow cells from MDS patients by RT-PCR was observed in the presence or absence of rapamycin. In result, exposure of rapamycin led to the disappearance of just the mutant gene band. This phenomenon possibly indicates that rapamycin only attacked the mutant GSTT-1 expressing clone.

MeSH terms

  • Bone Marrow Cells / pathology
  • Drug Delivery Systems
  • Glutathione Transferase / drug effects
  • Glutathione Transferase / genetics
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Mutation
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / enzymology*
  • Myelodysplastic Syndromes / pathology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sirolimus / pharmacology*

Substances

  • RNA, Messenger
  • glutathione S-transferase T1
  • Glutathione Transferase
  • Sirolimus