Characteristics of Cohesin Mutation in Acute Myeloid Leukemia and Its Clinical Significance.

Caixia Han,Li Yu,Xuefeng Gao,Yonghui Li,Li Zhang,Erna Yang,Juan Zhang

doi:10.3389/fonc.2021.579881

Caixia Han, Li Yu + Show 5 more

Open Access

https://doi.org/10.3389/fonc.2021.579881

Copy DOI

Abstract

The occurrence of gene mutation is a major contributor to the initiation and propagation of acute myeloid leukemia (AML). Accumulating evidence suggests that genes encoding cohesin subunits have a high prevalence of mutations in AML, especially in the t(8;21) subtype. Therefore, it is important to understand how cohesin mutations contribute to leukemogenesis. However, the fundamental understanding of cohesin mutation in clonal expansion and myeloid transformation in hematopoietic cells remains ambiguous. Previous studies briefly introduced the cohesin mutation in AML; however, an in-depth summary of mutations in AML was not provided, and the correlation between cohesin and AML1-ETO in t (8;21) AML was also not analyzed. By summarizing the major findings regarding the cohesin mutation in AML, this review aims to define the characteristics of the cohesin complex mutation, identify its relationships with co-occurring gene mutations, assess its roles in clonal evolution, and discuss its potential for the prognosis of AML. In particular, we focus on the function of cohesin mutations in RUNX1-RUNX1T1 fusion.

Highlights

It has become apparent that acute myeloid leukemia (AML) is induced by the cooperative action of deregulated genes that alter cell proliferation and differentiation
We found that the majority of STAG2 and RAD21 mutations were nonsense and frameshift in all the AML subtypes (Figure 2A), suggesting that cohesin mutations resulted in a decrease or loss of the cohesin function
By summarizing the positions for the identified cohesin mutation genes that reported in t(8;21) AML patients (Figure 2B), we found that the mutation sites of RAD21 were present over the whole coding section

Summary

Introduction

It has become apparent that acute myeloid leukemia (AML) is induced by the cooperative action of deregulated genes that alter cell proliferation and differentiation. Chromosomal translocations and/or gene mutations are the most common chromosome abnormalities in AML. AML with chromosomal rearrangements t(8;21) (q22;q22) can trigger the generation of the aberrant oncogenic fusion protein AML1-ETO [3, 4]. AML1-ETO alone is not sufficient to induce the onset of leukemia, and additional genetic/epigenetic abnormalities are required [5, 6]. Mutations in multiple driver genes have been identified in AML patients with AML1-ETO fusion [7,8,9], further indicating that AML1-ETO required additional genetic/epigenetic abnormalities to induce t(8;21) leukemogenesis. Cohesin Mutation in AML investigations, through genome-wide sequencing, revealed recurrent mutations in the cohesin complex genes in AML patients, especially in the t(8;21) subtype [10,11,12,13]. Only few studies have investigated the role of cohesin mutation in the pathogenesis of AML

Objectives

Findings

Conclusion