Dataset Information

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

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.

SUBMITTER: Gao Y

PROVIDER: S-EPMC9599642 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Gao Yan Y Zhou Jia-Fan JF Mao Jia-Ying JY Jiang Lu L Li Xue-Ping XP

Biomolecules 20220923 10

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+CD117bri myeloblasts, were found to be prognostic in RUNX1-RUNX1T1 AML. However, the clinical and genetic fea ...[more]

PMID: 36291567

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Project description:It is known that growth hormone (GH) is expressed in immune cells, where it exerts immunomodulatory effects. However, the mechanisms of expression and release of GH in the immune system remain unclear. We analyzed the effect of growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), ghrelin (GHRL), and somatostatin (SST) upon GH mRNA expression, intracellular and released GH, Ser133-phosphorylation of CREB (pCREBS133), intracellular Ca2+ levels, as well as B-cell activating factor (BAFF) mRNA expression in bursal B-lymphocytes (BBLs) cell cultures since several GH secretagogues, as well as their corresponding receptors (-R), are expressed in B-lymphocytes of several species. The expression of TRH/TRH-R, ghrelin/GHS-R1a, and SST/SST-Rs (Subtypes 1 to 5) was observed in BBLs by RT-PCR and immunocytochemistry (ICC), whereas GHRH/GHRH-R were absent in these cells. We found that TRH treatment significantly increased local GH mRNA expression and CREB phosphorylation. Conversely, SST decreased GH mRNA expression. Additionally, when added together, SST prevented TRH-induced GH mRNA expression, but no changes were observed in pCREBS133 levels. Furthermore, TRH stimulated GH release to the culture media, while SST increased the intracellular content of this hormone. Interestingly, SST inhibited TRH-induced GH release in a dose-dependent manner. The coaddition of TRH and SST decreased the intracellular content of GH. After 10 min. of incubation with either TRH or SST, the intracellular calcium levels significantly decreased, but they were increased at 60 min. However, the combined treatment with both peptides maintained the Ca2+ levels reduced up to 60-min. of incubation. On the other hand, BAFF cytokine mRNA expression was significantly increased by TRH administration. Altogether, our results suggest that TRH and SST are implicated in the regulation of GH expression and release in BBL cultures, which also involve changes in pCREBS133 and intracellular Ca2+ concentration. It is likely that TRH, SST, and GH exert autocrine/paracrine immunomodulatory actions and participate in the maturation of chicken BBLs.

Dataset Information

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

Publications

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

Similar Datasets

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