RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2

PLoS One. 2016 Mar 23;11(3):e0152142. doi: 10.1371/journal.pone.0152142. eCollection 2016.

Abstract

Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Blotting, Western
  • Chromatin Immunoprecipitation
  • Disease Progression
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Real-Time Polymerase Chain Reaction
  • Retinol-Binding Proteins, Cellular / physiology*
  • Up-Regulation

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RBP2 protein, human
  • Retinol-Binding Proteins, Cellular

Grants and funding

The authors thank the grant support from the National Natural Science Foundation of China (nos. 81470318, 81170514, 30971151), the cross training program of Shandong University (nos. 2015JC052), the National Basic Research Program of China (no. 973 Program 2012CB911202) and the project of Shandong province science and technology development plans (nos. 2014GSF118114).