Frontiers in Hematology · Published 2026-06-26 · DOI 10.3389/frhem.2026.1850831
Arunim Shah, Arun Kumar Trivedi, Chandra Prakash Chaturvedi
Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by the accumulation of immature myeloid cells in the bone marrow. Despite advances in genomic profiling and targeted therapies, patient outcomes remain poor because of high relapse rates and the persistence of therapy-resistant leukemic stem cells. Growing evidence underscores the critical role of the bone marrow microenvironment in regulating leukemia progression, survival, and treatment response. Normally, the bone marrow niche supports hematopoietic stem cell function through balanced interactions among stromal, vascular, immune, and metabolic components. In AML, leukemic cells actively remodel this niche to create an environment that promotes leukemia. This review outlines key cellular and molecular mechanisms underlying AML–niche interactions and their role in chemoresistance. We examine how BM niche components, including mesenchymal stromal cells, endothelial cells, immune cells, osteolineage cells, and adipocytes, contribute to leukemic growth by releasing cytokines, chemokines, and growth factors. The review further highlights key signaling pathways, including the CXCL12–CXCR4 axis, JAK/STAT, and adhesion-related signaling, which are essential for leukemic cell homing, survival, and drug resistance. Additionally, the roles of extracellular vesicles, metabolic changes, hypoxia, and immunosuppression, which further enhance the protective bone marrow environment, support the maintenance of leukemic stem cells and help them evade chemotherapy, leading to minimal residual disease and relapse, have been described. Finally, we discuss emerging therapies targeting the AML niche, including CXCR4 inhibitors, immune-based treatments, and strategies that disrupt stromal and vascular signaling. Addressing both leukemic cells and their supportive microenvironment may lead to more effective approaches to overcome chemoresistance and improve long-term outcomes in AML.
Abstract from DOAJ. Public domain (CC0 1.0).
Read the article at the publisher →
Shah, A., Trivedi, A., Chaturvedi, C. (2026). Crosstalk of factors underlying bone marrow niche-mediated chemoprotection in acute myeloid leukemia. Frontiers in Hematology. https://doi.org/10.3389/frhem.2026.1850831