Identification of the Thyrotropin-Releasing Hormone (TRH) as a Novel Biomarker in the Prognosis for Acute Myeloid Leukemia

Yan Gao; Jia-Fan Zhou; Jia-Ying Mao; Lu Jiang; Xue-Ping Li

doi:10.3390/biom12101359

Identification of the Thyrotropin-Releasing Hormone (TRH) as a Novel Biomarker in the Prognosis for Acute Myeloid Leukemia

Biomolecules. 2022 Sep 23;12(10):1359. doi: 10.3390/biom12101359.

Authors

Yan Gao^{1

2}, Jia-Fan Zhou³, Jia-Ying Mao^{1

2}, Lu Jiang⁴, Xue-Ping Li^{2

5}

Affiliations

¹ Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
² State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
³ Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
⁴ Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁵ Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Abstract

Acute myeloid leukemia (AML) is a biologically and genetically heterogeneous hematological malignance with an unsatisfactory risk stratification system. Recently, through the novel single-cell RNA sequencing technology, we revealed heterogeneous leukemia myeloblasts in RUNX1-RUNX1T1 AML. Thyrotropin-releasing hormone (TRH), as biomarkers of CD34⁺CD117^bri myeloblasts, were found to be prognostic in RUNX1-RUNX1T1 AML. However, the clinical and genetic features of TRH in AML patients are poorly understood. Here, with data from TCGA AML, TRH was found to be downregulated in patients older than 60 years old, with DNMT3A and NPM1 mutations, while overexpressed in patients with KIT mutations. This was further validated in three other cohorts of primary AML including Beat AML (n = 223), GSE6891 (n = 461), and GSE17855 (n = 237). Furthermore, we demonstrated that the expression of TRH in AML could be used to improve the ELN 2017 risk stratification system. In conclusion, our preliminary analysis revealed that TRH, a novel biomarker for AML patients, could be used to evaluate the survival of AML.

Keywords: TRH expression; acute myeloid leukemia; biomarkers; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Core Binding Factor Alpha 2 Subunit* / genetics
Humans
Leukemia, Myeloid, Acute* / diagnosis
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / metabolism
Middle Aged
Mutation
Nuclear Proteins / genetics
Thyrotropin-Releasing Hormone / genetics

Substances

Core Binding Factor Alpha 2 Subunit
Thyrotropin-Releasing Hormone
Biomarkers
Nuclear Proteins

Grants and funding

This work was supported by the Guangdong Basic and Applied Basic Research Foundation (2021A1515110012) and the Shanghai Rising-Star Program (22QA1405600).