Tcf-1 gene silence suppresses downstream gene expression in CD4(+) T cells from bone marrow of aplastic anemia patients

Ann Hematol. 2012 Mar;91(3):353-8. doi: 10.1007/s00277-011-1314-0. Epub 2011 Sep 1.

Abstract

CD4(+) T cells play a crucial role in the pathogenesis of acquired aplastic anemia (AA). Tcf-1 gene regulates T cell development and function, and it is significantly upregulated in the bone marrow CD4(+) T cells from patients with acquired AA. To explore the role of Tcf-1 in the pathogenesis of AA, we knocked down Tcf-1 gene in CD4(+) T cells of AA patients and studied the effects of Tcf-1 silencing on its downstream gene expression. Upon transfection of psiRNA into marrow CD4(+) T cells from bone marrow of aplastic anemia patients, the expression of Tcf-1 was significantly knocked down; consequently, expressions of c-Myc and CD44 were also significantly reduced. Our results suggest that Tcf-1 may contribute to pathogenesis of AA by regulating downstream gene expression such as c-myc and CD44.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Aplastic / physiopathology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Separation
  • Cells, Cultured
  • Female
  • Gene Expression*
  • Gene Silencing
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T Cell Transcription Factor 1 / genetics*
  • T Cell Transcription Factor 1 / metabolism*
  • Young Adult

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • T Cell Transcription Factor 1
  • TCF7 protein, human