了解肿瘤基因改变、信号通路紊乱以及转化的造血细胞中被劫持的机制对于开发有效持久的液体肿瘤治疗策略至关重要。在这篇综述中，我们着重讨论了Hedgehog (HH)/GLI通路在血液恶性肿瘤中的具体参与以及其对多发性骨髓瘤、T细胞和B细胞淋巴瘤，以及淋巴和髓系白血病等癌症特征的表现和启动的作用。通过回顾在体内外针对血液恶性肿瘤的经典和非经典、独立于平滑蛋白依赖性的HH/GLI信号通路，并总结前期临床的体外和体内研究，我们着重阐明了HH/GLI信号通路通过控制细胞增殖、癌症干细胞命运、基因组不稳定性、微环境重塑和细胞存活等关键致癌过程和癌症标志物上的共同分子机制。此外，我们还总结了HH抑制剂的目前临床试验，并讨论了成功和挑战，以及未来联合治疗的机会。通过提供HH/GLI信号通路在液体肿瘤中的作用的概览，我们认为全面了解HH/GLI信号通路对癌症标志物形成的通用致癌效应至关重要，以确定肿瘤细胞及其重塑微环境中的关键易感性，为开发新型高效个体化联合疗法为血液恶性肿瘤铺平道路。版权所有 © 2023 美国血液学会。

Understanding the genetic alterations, disrupted signaling pathways, and hijacked mechanisms in oncogene-transformed hematologic cells is critical for the development of effective and durable treatment strategies against liquid tumors. In this review, we focus on the specific involvement of the Hedgehog (HH)/GLI pathway in the manifestation and initiation of various cancer features in hematological malignancies, including multiple myeloma, T- and B-cell lymphomas, and lymphoid and myeloid leukemias. By reviewing canonical and non-canonical, Smoothened-independent HH/GLI signaling and summarizing preclinical in vitro and in vivo studies in hematologic malignancies, we elucidate common molecular mechanisms by which HH/GLI signaling controls key oncogenic processes and cancer hallmarks such as cell proliferation, cancer stem cell fate, genomic instability, microenvironment remodeling, and cell survival. We also summarize current clinical trials with HH inhibitors and discuss successes and challenges as well as opportunities for future combined therapeutic approaches. By providing a bird's eye view of the role of HH/GLI signaling in liquid tumors, we suggest that a comprehensive understanding of the general oncogenic effects of HH/GLI signaling on the formation of cancer hallmarks is essential to identify critical vulnerabilities within tumor cells and their supporting remodeled microenvironment, paving the way for the development of novel and efficient personalized combination therapies for hematologic malignancies.Copyright © 2023 American Society of Hematology.