Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA.
Department of Chemistry and Biochemistry, College of Science and Mathematics, Rowan University, Glassboro, NJ 08028, USA.
Int J Mol Sci. 2021 May 27;22(11):5707. doi: 10.3390/ijms22115707.
Multiple myeloma (MM), a clonal plasma cell disorder, disrupts the bones' hematopoiesis and microenvironment homeostasis and ability to mediate an immune response against malignant clones. Despite prominent survival improvement with newer treatment modalities since the 2000s, MM is still considered a non-curable disease. Patients experience disease recurrence episodes with clonal evolution, and with each relapse disease comes back with a more aggressive phenotype. Bruton's Tyrosine Kinase (BTK) has been a major target for B cell clonal disorders and its role in clonal plasma cell disorders is under active investigation. BTK is a cytosolic kinase which plays a major role in the immune system and its related malignancies. The BTK pathway has been shown to provide survival for malignant clone and multiple myeloma stem cells (MMSCs). BTK also regulates the malignant clones' interaction with the bone marrow microenvironment. Hence, BTK inhibition is a promising therapeutic strategy for MM patients. In this review, the role of BTK and its signal transduction pathways are outlined in the context of MM.
多发性骨髓瘤(MM)是一种克隆性浆细胞疾病,它破坏了骨骼的造血和微环境的稳态,以及对恶性克隆体产生免疫反应的能力。尽管自 21 世纪以来,随着更新的治疗方式的出现,患者的生存状况有了显著改善,但 MM 仍被认为是一种不可治愈的疾病。患者会经历克隆进化的疾病复发,每次复发都会带来更具侵袭性的表型。布鲁顿酪氨酸激酶(BTK)一直是 B 细胞克隆疾病的主要靶点,其在克隆性浆细胞疾病中的作用正在积极研究中。BTK 是一种胞质激酶,在免疫系统及其相关恶性肿瘤中发挥重要作用。BTK 途径已被证明为恶性克隆体和多发性骨髓瘤干细胞(MMSCs)提供了生存能力。BTK 还调节恶性克隆体与骨髓微环境的相互作用。因此,BTK 抑制是 MM 患者有前途的治疗策略。在这篇综述中,概述了 BTK 及其信号转导途径在 MM 中的作用。