RRC ID 77365
Author Tsuzuki S, Taguchi O, Seto M.
Title Promotion and maintenance of leukemia by ERG.
Journal Blood
Abstract The Ets-related gene (ERG) located on human chromosome 21 encodes a transcription factor and is thought to be causally related to Down syndrome-associated acute megakaryocytic leukemia in childhood. In clinical adult leukemia, however, increased expression of ERG is indicative of poor prognosis in T-cell acute lymphoblastic leukemia and cytogenetically normal acute myeloid leukemia, although the involvement of ERG in the development of adult leukemia remains elusive. Here, we show that forced expression of ERG in adult BM cells alters differentiation and induces expansion of T and erythroid cells and increases frequencies of myeloid progenitors in mouse BM transplantation models. The expanded T cells then develop T-cell acute lymphoblastic leukemia after acquisition of mutations in the Notch1 gene. Targeted expression of ERG into B cells also altered differentiation and promoted growth of precursor B cells. Overall, these findings suggest a general role of ERG in promoting growth of adult hematopoietic cells in various lineages. In line with this, shRNA-mediated silencing of ERG expression attenuated growth of human leukemia cell lines of various lineages. Thus, ERG is capable of promoting the development of leukemia and is crucial for its maintenance.
Volume 117(14)
Pages 3858-68
Published 2011-4-7
DOI 10.1182/blood-2010-11-320515
PII S0006-4971(20)45311-X
PMID 21321361
MeSH Animals Cell Transformation, Neoplastic / genetics* Disease Progression Gene Expression Profiling Gene Expression Regulation, Leukemic Humans Leukemia / genetics* Leukemia / pathology Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Mice, Transgenic Microarray Analysis Neoplasm Transplantation Oncogene Proteins / genetics Oncogene Proteins / metabolism Oncogene Proteins / physiology* Transcription Factors Transcriptional Regulator ERG Transplantation, Heterologous Tumor Cells, Cultured
IF 17.794
Resource
Human and Animal Cells OP9(RCB1124)