Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

BMC Cancer, 02/09/2012

Ochoa-Hernandez AB et al. – To the knowledge of the authors, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T-lymphocytes inhibits cell proliferation. These results also support the possible function of WNT7A as a tumor suppressor gene as well as a therapeutic tool.

Methods

  • Analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, 4 leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects
  • Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative WNT7A expression
  • Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein
  • Cell proliferation was measured by addition of WST-1 to cell cultures

Results

  • WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (p [less than or equal to]0.001)
  • By restoring WNT7A expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth
  • Similar effect was observed when a recombinant human WNT7a protein was used
  • Restoration of WNT7A expression in Jurkat cells did not activate the canonical Wnt/beta-catenin pathway

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