Gu Ling, Liao Ping, Liu Hanmin
Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2022 Dec 19;12:1022979. doi: 10.3389/fonc.2022.1022979. eCollection 2022.
Although the prognosis for acute leukemia has greatly improved, treatment of relapsed/refractory acute leukemia (R/R AL) remains challenging. Recently, increasing evidence indicates that the bone marrow microenvironment (BMM) plays a crucial role in leukemogenesis and therapeutic resistance; therefore, BMM-targeted strategies should be a potent protocol for treating R/R AL. The targeting of cancer-associated fibroblasts (CAFs) in solid tumors has received much attention and has achieved some progress, as CAFs might act as an organizer in the tumor microenvironment. Additionally, over the last 10 years, attention has been drawn to the role of CAFs in the BMM. In spite of certain successes in preclinical and clinical studies, the heterogeneity and plasticity of CAFs mean targeting them is a big challenge. Herein, we review the heterogeneity and roles of CAFs in the BMM and highlight the challenges and opportunities associated with acute leukemia therapies that involve the targeting of CAFs.
尽管急性白血病的预后已大为改善，但复发/难治性急性白血病（R/R AL）的治疗仍然具有挑战性。最近，越来越多的证据表明，骨髓微环境（BMM）在白血病发生和治疗耐药中起关键作用；因此，针对BMM的策略应是治疗R/R AL的有效方案。实体瘤中癌症相关成纤维细胞（CAF）的靶向治疗已受到广泛关注并取得了一些进展，因为CAF可能在肿瘤微环境中起组织者的作用。此外，在过去10年中，CAF在BMM中的作用也受到了关注。尽管在临床前和临床研究中取得了一定成功，但CAF的异质性和可塑性意味着靶向它们是一项巨大挑战。在此，我们综述了CAF在BMM中的异质性和作用，并强调了涉及CAF靶向治疗的急性白血病疗法所面临的挑战和机遇。
