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从造血抑制到治疗耐药：白血病重塑骨髓血管微环境的双重结局

黄良桂, 赵奕君, 陈俊竹, 蒋琳加^*

中山大学中山医学院，中山大学孙逸仙纪念医院，广东省恶性肿瘤表观遗传与基因调控重点实验室，广州 510000

摘要

骨髓血管微环境主要由内皮细胞(endothelial cells, ECs)和间充质干细胞(mesenchymal stem/stromal cells, MSCs)构成，其通过调控造血干细胞(hematopoietic stem cells, HSCs)的静息、激活、增殖与分化，维持造血系统的稳态平衡。在白血病发生、发展过程中，恶性细胞重塑血管微环境，导致血管结构异常、内皮屏障完整性破坏、MSCs向促炎/促生存表型转化，以及ECs-MSCs-HSCs 之间正常信号网络的解体与异常通讯轴的建立。这些改变一方面破坏HSCs的正常生态位，导致骨髓衰竭相关的全血细胞减少；另一方面，重塑后的骨髓血管微环境转化为白血病细胞的庇护所，促进其增殖、迁移和耐药，最终驱动疾病复发与不良预后。本文系统阐述了白血病对骨髓血管微环境的重塑机制，在此基础上总结了靶向血管微环境的新兴治疗策略，旨在为克服白血病耐药瓶颈提供理论依据与转化方向。

关键词： 白血病; 血管微环境; 内皮细胞; 间充质干细胞; 化疗耐药

From hematopoietic suppression to therapy resistance: the dual outcomes of leukemia-induced remodeling of the bone marrow vascular microenvironment

HUANG Liang-Gui, ZHAO Yi-Jun, CHEN Jun-Zhu, JIANG Lin-Jia^*

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510000, China

Abstract

The bone marrow vascular microenvironment is primarily composed of endothelial cells (ECs) and mesenchymal stem/stromal cells (MSCs), which maintain hematopoietic homeostasis by regulating the quiescence, activation, proliferation, and differentiation of hematopoietic stem cells (HSCs). During leukemogenesis and disease progression, malignant cells remodel the vascular microenvironment, leading to aberrant vascular architecture, disruption of endothelial barrier integrity, phenotypic conversion of MSCs toward a pro-inflammatory/pro-survival state, and the dismantling of normal signaling networks among ECs, MSCs, and HSCs, alongside the establishment of aberrant communication axes. These alterations, on one hand, disrupt the supportive HSC niche, resulting in bone marrow failure-associated pancytopenia. On the other hand, the remodeled vascular microenvironment transforms into a sanctuary that promotes leukemia cell proliferation, migration, and drug resistance, ultimately driving disease relapse and poor prognosis. This review systematically elucidates the mechanisms underlying leukemia-induced remodeling of the bone marrow vascular microenvironment and, based on these findings, summarizes emerging therapeutic strategies targeting the vascular microenvironment, aiming to provide a theoretical foundation and translational directions for overcoming therapy resistance in leukemia.

Key words: Leukemia; vascular microenvironment; endothelial cells; mesenchymal stem/stromal cells; chemotherapy resistance

收稿日期：　　录用日期：

通讯作者：蒋琳加　　E-mail:

DOI: 10.13294/j.aps.2026.0080

引用本文：

黄良桂, 赵奕君, 陈俊竹, 蒋琳加. 从造血抑制到治疗耐药：白血病重塑骨髓血管微环境的双重结局[J]. 生理学报 2026; 78 (4): 815-824.

HUANG Liang-Gui, ZHAO Yi-Jun, CHEN Jun-Zhu, JIANG Lin-Jia. From hematopoietic suppression to therapy resistance: the dual outcomes of leukemia-induced remodeling of the bone marrow vascular microenvironment. Acta Physiol Sin 2026; 78 (4): 815-824 (in Chinese with English abstract).