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血管生成素1(ANGPT1)和同源盒A3(HOXA3)在急性髓系白血病中的高表达及其调控机制

High expression and regulatory mechanisms of ANGPT1 and HOXA3 in acute myeloid leukemia.

作者信息

Xuan Fan, Liu Na, Zhang Bao-Xi, Wen Wen-Xiao, Wang Yong-Cai, Zhang Hui-Feng, Wu Xiao-Li

机构信息

Department of Pediatrics Hematology-Oncology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.

Department of Pediatrics Hematology-Oncology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.

出版信息

Bull Cancer. 2025 Sep;112(9):948-960. doi: 10.1016/j.bulcan.2025.01.014. Epub 2025 Mar 18.

DOI:10.1016/j.bulcan.2025.01.014
PMID:40107921
Abstract

OBJECTIVE

Acute Myeloid Leukemia (AML) is a type of leukemia characterized by the malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study aims to investigate the role of ANGPT1 and HOXA3 in the leukemia cell line KG-1a.

METHODS

The expression patterns of ANGPT1 and HOXA3 in AML patients were determined by analyzing the TCGA database and clinical samples. Experiments were conducted using the KG-1a cell line, including flow cytometry and SA-β-Gal staining, to knock down ANGPT1 and HOXA3 and evaluate their functions.

RESULTS

ANGPT1 and HOXA3 were found to be highly expressed in AML patients. Knocking down ANGPT1 and HOXA3 promoted apoptosis and senescence in KG-1a cells by inhibiting proliferation-related genes and upregulating apoptosis-related genes. There is a reciprocal regulatory relationship between ANGPT1 and HOXA3, forming a positive feedback loop. Treatment with ATRA downregulated the expression of HOXA3 and induced apoptosis in KG-1a cells, highlighting the importance of HOXA3 as a therapeutic target in AML.

CONCLUSION

ANGPT1 and HOXA3 are highly expressed in AML, and knocking them down can promote apoptosis and senescence in leukemia cells. They exhibit a mutual regulatory relationship, forming a positive feedback loop. These findings contribute to a better understanding of the functional roles and regulatory mechanisms of ANGPT1 and HOXA3, and provide new scientific evidence for the treatment and prognosis improvement of AML patients.

摘要

目的

急性髓系白血病(AML)是一种以骨髓中造血干细胞恶性克隆增殖为特征的白血病。本研究旨在探讨血管生成素1(ANGPT1)和同源盒A3(HOXA3)在白血病细胞系KG-1a中的作用。

方法

通过分析癌症基因组图谱(TCGA)数据库和临床样本,确定AML患者中ANGPT1和HOXA3的表达模式。使用KG-1a细胞系进行实验,包括流式细胞术和衰老相关β-半乳糖苷酶(SA-β-Gal)染色,以敲低ANGPT1和HOXA3并评估它们的功能。

结果

发现ANGPT1和HOXA3在AML患者中高表达。敲低ANGPT1和HOXA3通过抑制增殖相关基因和上调凋亡相关基因,促进KG-1a细胞的凋亡和衰老。ANGPT1和HOXA3之间存在相互调节关系,形成正反馈环。全反式维甲酸(ATRA)处理下调HOXA3的表达并诱导KG-1a细胞凋亡,突出了HOXA3作为AML治疗靶点的重要性。

结论

ANGPT1和HOXA3在AML中高表达,敲低它们可促进白血病细胞的凋亡和衰老。它们表现出相互调节关系,形成正反馈环。这些发现有助于更好地理解ANGPT1和HOXA3的功能作用和调节机制,并为AML患者的治疗和预后改善提供新的科学证据。

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