Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia

Toni Grönroos,Saara Laukkanen,Olli Lohi,Yanara Marincevic-Zuniga,Merja Heinäniemi,Samuli Rounioja,Laura Oksa,Jessica Nordlund,Artturi Mäkinen,Timo Paavonen,Juha Mehtonen,Virva Pohjolainen,Atte Nikkilä

doi:10.1038/s41598-020-58970-z

Abstract

Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features. We sought to identify the transcription factors exhibiting altered and subtype-specific expression patterns in B-ALL and report here that SOX11, a developmental and neuronal transcription factor, is aberrantly expressed in the ETV6-RUNX1 and TCF3-PBX1 subtypes of acute B-cell leukemias. We show that a high expression of SOX11 leads to alterations of gene expression that are typically associated with cell adhesion, migration, and differentiation. A high expression is associated with DNA hypomethylation at the SOX11 locus and a favorable outcome. The results indicate that SOX11 expression marks a group of patients with good outcomes and thereby prompts further study of its use as a biomarker.

Highlights

Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features
SOX11 is overexpressed in acute lymphoblastic leukemias
We report here that SOX11, a developmental and neuronal TF6, is overexpressed in the E/R and T/P subtypes of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and in novel E/R-like, IKZF1 N159Y, MEF2D rearrangement, and DUX4 rearrangement subtypes

Summary

Introduction

Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features. SOX11 is normally expressed in the developing central nervous system of the embryo, in keratinocytes, and in some other epithelial tissues[1,6,7,8]. It is expressed in ovarian and breast cancer, in which both tumor suppressor and oncogenic functions have been suggested[9,10]. Another study reported the strong nuclear expression of SOX11 in a single B-cell and five T-cell lymphoblastic lymphoma/leukemias[13]. The function of SOX11 in leukemias and its clinical significance as a biomarker were further explored

Methods

Results

Conclusion