Novel transcriptional targets of ETV6, a transcription factor frequently altered in childhood pre-B acute lymphoblastic leukemia

Daniel Sinnett

doi:10.15226/csroa.2016.00124

Abstract

Novel transcriptional targets of ETV6, a transcription factor frequently altered in childhood pre-B acute lymphoblastic leukemia

Highlights

Acute Lymphoblastic Leukemia (ALL) is the most frequent pediatric cancer in children and accounts for ~25% of all pediatric cancers [1]
The expression of the ETV6-RUNX1chimera is under the control of the ETV6 promoter, which leads to the expression of a chimeric transcription factor composed of the N-terminal part of ETV6 fused to the near complete RUNX1 protein
We show that SSPHK1 and prostaglandin E2 receptor EP4 subtype (PTGER4) are direct ETV6 transcriptional targets with ETV6-mediated transcriptional regulation requiring consensus Ets-Binding Sites (EBS) in the proximal promoter region

Summary

Introduction

Acute Lymphoblastic Leukemia (ALL) is the most frequent pediatric cancer in children and accounts for ~25% of all pediatric cancers [1]. The t(12;21) translocation is the most common genetic aberration in childhood pre-B ALL, occurring in 25% of pre-B ALL cases [2]. This translocation leads to the formation of the ETV6RUNX1 chimera, an in-frame fusion of an ETV6 (erythroblast transformation-specific variant 6) allele with an allele of RUNX1 (runt-related transcription factor 1) [3, 4]. Using inducible gene disruption and ETV6-/- chimeric mice, ETV6 was shown to be involved in the survival/homing of the hematopoietic stem cells and in the differentiation of the megakaryocytic precursors within the bone marrow microenvironment [8, 9]

Methods

Results

Conclusion