RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

Xiaoming Wang,Chunyan Chen,Yue Fu,Jihui Jia,Yuan Yu,Minran Zhou,Jin Chen,Ting Sun,Xuemei Qin,Chunhua Song

doi:10.1371/journal.pone.0152142

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.

Highlights

Acute lymphoblastic leukemia (ALL), a clonal malignancy of lymphocyte precursors, is a lifethreatening neoplasm characterized by uncontrolled growth and leukemic expansion of immature lymphoblastic progenitor cells [1,2,3]
We identified a critical function of retinoblastoma binding protein-2 (RBP2) in mediating apoptosis and proliferation in ALL
Our data indicated that RBP2 played an oncogenic role in adult ALL and that its overexpression correlated with the progression of ALL

Summary

Introduction

Acute lymphoblastic leukemia (ALL), a clonal malignancy of lymphocyte precursors, is a lifethreatening neoplasm characterized by uncontrolled growth and leukemic expansion of immature lymphoblastic progenitor cells [1,2,3]. This disease is prevalent in both children and adults, with a peak incidence between the ages of 2 to 5 years, and constitutes 15% of adult leukemias [1, 4]. Leukemia was thought to stem primarily from genetic alterations, which affect proliferation, differentiation, apoptosis and gene transcription of leukemic cells. MicroRNA-193b-3p acts as a tumor suppressor in T-cell acute lymphoblastic leukemia [8], and miR-17~92 is downregulated in BCR-ABL-positive human ALL samples [9]. 5-aza-20-deoxycytidine (decitabine) has been used to target hypermethylation clinically

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