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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

Received: 　　Accepted:

Corresponding author: 蒋琳加　　E-mail:

DOI: 10.13294/j.aps.2026.0080

Citing This Article：

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).