尽管近年来治疗血液恶性肿瘤取得了一些进展，但复发问题仍然持续存在。造成复发的主要原因之一是骨髓微环境为恶性细胞提供庇护所。这些细胞与骨髓组分如成骨细胞、基质细胞、细胞外基质蛋白和可溶性因子等相互作用。这些相互作用通过细胞表面蛋白（如细胞黏附分子）介导的细胞间信号转导诱导骨髓微环境诱导的化疗保护（BMC）的发展。虽然这些细胞黏附分子进行了广泛的研究，包括开发靶向治疗，但在血液恶性肿瘤中很少关注另一种同样重要的介导骨髓相互作用的细胞表面蛋白家族——跨膜4超家族（四膜蛋白家族；TSPANs）。根据对实体肿瘤的众多研究，已经证明TSPANs在介导微环境相互作用和转移中起重要作用。最近，有证据表明它们在血液恶性肿瘤中可能在细胞黏附、骨髓定植、细胞内信号转导和恶性血液细胞中干细胞动态调控方面发挥作用。这些效应中，许多是通过与TSPAN富集的微区域上的细胞黏附分子和其他受体的相互作用实现。这表明TSPANs在介导血液恶性肿瘤中的BMC中起着重要作用，因此可作为治疗靶点。在本综述中，我们将讨论TSPAN在血液细胞中的结构和功能，它们与不同细胞表面和信号蛋白的相互作用，以及可能的靶向/抑制其效应的方法。©2023由美国血液学会版权所有。采用创作共用署名-非商业性-禁止演绎4.0国际许可协议（CC BY-NC-ND 4.0），只允许非商业性、无派生物使用，并需署名。其他所有权利保留。

Despite recent advances in the treatment of hematologic malignancies, relapse still remains a consistent issue. One of the primary contributors to relapse is the bone marrow microenvironment providing a sanctuary to malignant cells. These cells interact with bone marrow components such as osteoblasts and stromal cells, extracellular matrix proteins, and soluble factors. These interactions, mediated by the cell surface proteins like cellular adhesion molecules (CAMs), induce intracellular signaling that leads to the development of bone marrow microenvironment-induced chemoprotection (BMC). Although extensive study has gone into these CAMs, including the development of targeted therapies, very little focus in hematologic malignancies has been put on a family of cell surface proteins that are just as important for mediating bone marrow interactions: the transmembrane 4 superfamily (tetraspanins; TSPANs). TSPANs are known to be important mediators of microenvironmental interactions and metastasis based on numerous studies in solid tumors. Recently, evidence of their possible role in hematologic malignancies, specifically in the regulation of cellular adhesion, bone marrow homing, intracellular signaling, and stem cell dynamics in malignant hematologic cells has come to light. Many of these effects are facilitated by associations with CAMs and other receptors on the cell surface in TSPAN-enriched microdomains. This could suggest that TSPANs play an important role in mediating BMC in hematologic malignancies and could be used as therapeutic targets. In this review, we discuss TSPAN structure and function in hematologic cells, their interactions with different cell surface and signaling proteins, and possible ways to target/inhibit their effects.© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.