In April 2023, a study led by Professor Tao Cheng from Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College was published in the international academic journal ——Blood Science . The title of the study is "Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia". This study elucidates the interactions between leukemia cells and the bone marrow (BM) vascular niche play a crucial role in the persistence of chemotherapy resistance in Acute myeloid leukemia (AML). Targeting the dynamic communication between leukemia cells and the altered vascular niche presents a promising strategy for overcoming this challenge.Acute myeloid leukemia (AML) represents a significant challenge in cancer treatment, primarily due to the resilience of leukemia stem cells (LSCs) within the bone marrow (BM) niche against conventional chemotherapy, often resulting in disease relapse. The BM niche, comprising various cell types including endothelial cells (ECs) and perivascular mesenchymal stem cells, plays a pivotal role in the survival and differentiation of hematopoietic stem cells (HSCs). This study focuses on elucidating the complex interactions between AML cells and the BM vascular niche, aiming to uncover new avenues for targeted therapies to overcome chemotherapy resistance in AML.
The study employed a sophisticated real-time cell cycle-tracking mouse model of AML (Fucci-MA9) to explore the dynamics between quiescent leukemia cells and endothelial cells within the BM niche during disease progression, chemotherapy, and subsequent relapse. RNA-sequencing was utilized to dissect the transcriptomic profiles of both ECs and quiescent leukemia cells at different disease phases, providing a comprehensive understanding of the cellular and molecular changes occurring within the BM niche.
The study opens several avenues for further research, including the identification and validation of molecular targets within the leukemia cell-EC interaction axis. Investigating the role of other niche components, such as mesenchymal stem cells, in supporting leukemia survival and resistance could also yield new therapeutic targets. Additionally, translating these findings into clinical settings by developing targeted therapies in human AML patients represents a critical next step.
Reference：Chang X, et al, Cheng, T; Cheng, H. Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia. Blood Science . 2023 Apr 19;5(2):92-100.
