Midkine and TNFSF10 as downstream molecules of type I interferon are involved in the treatment of myelofibrosis.

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects Pub Date : 2025-09-29 DOI:10.1016/j.bbagen.2025.130863

Yaoyao Chen, Fanxiang Yin, Xiaoqian Wang, Huilin Zhang, Ping Tang, Mengjiao Xue, Nannan Sun, Jin Li, Chang Chen, Bingjie Wang, Qingxuan Xin, Juanxia Zhou, Yingmei Li, Shuya Wang, Shaohua Yan, Jiani Li, Yunling Zhu, Bo Qin, Baohong Yue, Yong Jiang, Rongqun Guo

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引用次数: 0

Abstract

Myelofibrosis (MF), a myeloproliferative neoplasm, remains incurable for most patients. Although some individuals are eligible for allogeneic hematopoietic stem cell transplantation, current therapies generally slow disease progression rather than achieve a cure. In this study, we found that type I interferon (IFN) treatment enhances midkine (MDK) expression, and MDK is involved in the differentiation and maturation of progenitor cells. Notably, MDK treatment drives tumor cells into the cell cycle, thereby increasing the therapeutic effect of busulfan. Furthermore, MDK promotes osteogenic differentiation of mesenchymal stem cells (MSC), contributing to the remodeling of the bone marrow microenvironment. In addition, type I IFN upregulates TNFSF10, leading to tumor cell death through mutual killing.

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Midkine和TNFSF10作为I型干扰素的下游分子参与骨髓纤维化的治疗。

骨髓纤维化（MF）是一种骨髓增生性肿瘤，对大多数患者来说仍然是无法治愈的。虽然有些人适合异体造血干细胞移植，但目前的治疗方法通常会减缓疾病的进展，而不是实现治愈。在本研究中，我们发现I型干扰素（IFN）处理可增强midkine （MDK）的表达，而MDK参与了祖细胞的分化和成熟。值得注意的是，MDK治疗可使肿瘤细胞进入细胞周期，从而提高了布苏凡的治疗效果。此外，MDK促进间充质干细胞（MSC）的成骨分化，有助于骨髓微环境的重塑。此外，I型IFN上调TNFSF10，通过相互杀伤导致肿瘤细胞死亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. General subjects 生物-生化与分子生物学

CiteScore

6.40

自引率

0.00%

发文量

139

审稿时长

30 days

期刊介绍： BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.