Department of Hematology, Key Laboratory of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
J Transl Med. 2022 Jul 6;20(1):304. doi: 10.1186/s12967-022-03500-w.
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. SEMA4D is a 150 kDa transmembrane protein that belongs to the IV class of the subfamily of semaphorin family. Previous studies have reported that SEMA4D is a multifunctional target in many solid tumors, involving multiple physiological systems, and there are emerging therapies to target these pathways. The role of SEMA4D in AML has not yet been explored.
The SEMA4D expression prolile, clinical data and potential prognostic analysis were acquired via the cBioPortal and GEPIA databases. SEMA4D expression was measured using real-time quantitative PCR and western blot. Cell counting kit-8 (CCK8) and flow cytometry were used to evaluate the malignant biological characteristics.
We observed that SEMA4D was increased in AML patients and correlated with risk stratification and prognosis. Moreover, SEMA4D promotes the proliferation and inhibits apoptosis of AML cells by binding to its receptor, PlexinB1, and reduces the sensitivity of AML cells to daunorubicin. In addition, SEMA4D/PlexinB1 promotes the proliferation and survival of AML cells by activating the PI3K/Akt signaling pathway. VX15/2503, an anti-SEMA4D antibody, can inhibit the proliferation of AML cells in xenograft mouse models, thereby inhibiting the development of AML.
SEMA4D will serve as a unique predictive biomarker and a possible therapeutic target in AML.
急性髓系白血病（AML）是成人中最常见的急性白血病类型。SEMA4D 是一种 150 kDa 的跨膜蛋白，属于信号素家族的 IV 类亚家族。先前的研究表明，SEMA4D 是许多实体瘤中的多功能靶标，涉及多个生理系统，并且有新兴的疗法来针对这些途径。SEMA4D 在 AML 中的作用尚未得到探索。
通过 cBioPortal 和 GEPIA 数据库获取 SEMA4D 表达谱、临床数据和潜在预后分析。使用实时定量 PCR 和 Western blot 测量 SEMA4D 表达。细胞计数试剂盒-8（CCK8）和流式细胞术用于评估恶性生物学特征。
我们观察到 AML 患者中 SEMA4D 增加，并与风险分层和预后相关。此外，SEMA4D 通过与其受体 PlexinB1 结合促进 AML 细胞的增殖并抑制其凋亡，并降低 AML 细胞对柔红霉素的敏感性。此外，SEMA4D/PlexinB1 通过激活 PI3K/Akt 信号通路促进 AML 细胞的增殖和存活。抗 SEMA4D 抗体 VX15/2503 可抑制异种移植小鼠模型中 AML 细胞的增殖，从而抑制 AML 的发展。
SEMA4D 将作为 AML 中独特的预测生物标志物和可能的治疗靶标。
