Karches Center for Oncology Research, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.
Departments of Molecular Medicine and of Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
Hematol Oncol. 2023 Jun;41 Suppl 1:119-128. doi: 10.1002/hon.3144.
The leukemic B cells from patients with chronic lymphocytic leukemia (CLL) require interactions with non-malignant cells and matrix in the tissue microenvironment to survive and grow. These interactions are mediated through the B-cell antigen receptor (BCR), C-X-C chemokine receptor type 4 (CXCR4), and a variety of integrins, including VLA-4. Exciting each receptor type leads to activation of Bruton's tyrosine kinase (BTK), which in turn helps initiate trophic signals that prevent cell death and promote cell activation and growth as well as allowing cells to return to anatomic sites for rescue signals. These represent the two major functional actions targeted by inhibitors of Btk. Here we relate some of the therapeutic actions of ibrutinib, a Btk inhibitor that is extremely helpful for patients with CLL, certain Diffuse Large B-cell Lymphomas (ABC type), and other non-Hodgkin's lymphomas, emphasizing that ibrutinib's value results from blocking beneficial signals, not by inducing lethal ones.
慢性淋巴细胞白血病 (CLL) 患者的白血病 B 细胞需要与组织微环境中的非恶性细胞和基质相互作用才能存活和生长。这些相互作用是通过 B 细胞抗原受体 (BCR)、C-X-C 趋化因子受体 4 (CXCR4) 和各种整合素（包括 VLA-4）介导的。每种受体类型的激活都会导致 Bruton 酪氨酸激酶 (BTK) 的激活，BTK 反过来有助于启动营养信号，防止细胞死亡并促进细胞激活和生长，以及使细胞返回到解剖部位以获取救援信号。这些是 BTK 抑制剂靶向的两种主要功能作用。在这里，我们将介绍伊布替尼（一种 BTK 抑制剂）的一些治疗作用，伊布替尼对 CLL、某些弥漫性大 B 细胞淋巴瘤（ABC 型）和其他非霍奇金淋巴瘤患者非常有帮助，强调伊布替尼的价值来自于阻断有益信号，而不是诱导致命信号。
