Twist Family BHLH Transcription Factor 1 is Required for the Maintenance of Leukemia Stem Cell in MLL-AF9 Acute Myeloid Leukemia

Overview

Journal Haematologica

Specialty Hematology

Date 2023 Sep 28

PMID 37767575

Authors

Nan Wang

Jing Yin

Na You

Wenqi Zhu

Nini Guo

Xiaoyan Liu

Peiwen Zhang

Wanling Huang

Yueqiao Xie

Qian Ren

Xiaotong Ma

Affiliations

Soon will be listed here.

Abstract

Leukemia stem cells (LSC) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSC of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in a H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSC, and that it promotes the initiation and maintenance of MLL-AF9-mediated AML. In addition, TWIST1 directly interacts and collaborates with HOXA9 in inducing AML in mice. Mechanistically, TWIST1 exerts its oncogenic function by activating the WNT5a/RAC1 axis. Collectively, our study uncovers a critical role of TWIST1 in LSC function and provides new mechanistic insights into the pathogenesis of MLL-AF9+ AML.

Citing Articles

The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.

Cuevas D, Amigo R, Agurto A, Heredia A, Guzman C, Recabal-Beyer A Biomedicines. 2024; 12(8).

PMID: 39200378 PMC: 11351244. DOI: 10.3390/biomedicines12081915.

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.

Mirjat D, Kashif M, Roberts C Int J Mol Sci. 2023; 24(24).

PMID: 38139368 PMC: 10743446. DOI: 10.3390/ijms242417539.

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