Inhibition of PRAME expression causes cell cycle arrest and apoptosis in leukemic cells

Leuk Res. 2011 Sep;35(9):1219-25. doi: 10.1016/j.leukres.2011.04.005. Epub 2011 May 7.

Abstract

The preferentially expressed antigen of melanoma (PRAME) is known as a tumor-associated antigen, but its function in leukemia remains unclear. We investigated the function with small interfering RNA (siRNA)-induced knockdown of PRAME in a K562 cell line. After PRAME siRNA transfection, proliferation was suppressed and cell cycle analysis showed G(0)/G(1) arrest, followed by apoptosis. PRAME siRNA-treated cells also showed changes in the genes affecting erythroid differentiation. We examined the PRAME expression levels and the S phase population of 32 acute leukemia patients at the time of diagnosis and relapse. An increase of the S phase population was accompanied by an increase of PRAME expression at relapse. Our results suggest that PRAME plays an important role in disease progression in acute leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Antigens, Neoplasm / physiology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Disease Progression
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • K562 Cells
  • Leukemia / genetics
  • Leukemia / pathology*
  • RNA, Small Interfering / pharmacology*

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • PRAME protein, human
  • RNA, Small Interfering