Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Dana 2054, Boston, MA 02215, USA.
Hematol Oncol Clin North Am. 2020 Apr;34(2):441-448. doi: 10.1016/j.hoc.2019.10.005. Epub 2019 Dec 11.
BCL-2 is an antiapoptotic protein that plays a critical role acute and chronic leukemias. Venetoclax is an orally selective BCL-2 inhibitor and BH3 mimetic approved in chronic lymphocytic leukemia and in combination with low dose cytarabine or hypomethylating agent in acute myeloid leukemia for the treatment of patients unfit for intensive chemotherapy. This article reviews the biology of BCL-2, focusing on its relationship to the myeloid microenvironment, and discusses the rationale for BCL-2 inhibition in myelodysplastic syndrome (MDS). Clinical trials testing venetoclax in MDS patients are under way. Potential biomarkers for clinical response to BCL-2 inhibition are discussed. Therapeutic opportunities for venetoclax in the therapeutic landscape of MDS are explored.
BCL-2 是一种抗凋亡蛋白，在急性和慢性白血病中起着关键作用。Venetoclax 是一种口服选择性 BCL-2 抑制剂和 BH3 模拟物，已在慢性淋巴细胞白血病中获得批准，并与低剂量阿糖胞苷或低甲基化剂联合用于治疗不适合强化化疗的急性髓系白血病患者。本文综述了 BCL-2 的生物学特性，重点讨论了其与髓系微环境的关系，并讨论了 BCL-2 抑制在骨髓增生异常综合征 (MDS) 中的作用机制。目前正在进行 Venetoclax 治疗 MDS 患者的临床试验。讨论了对 BCL-2 抑制临床反应的潜在生物标志物。探讨了 Venetoclax 在 MDS 治疗领域的治疗机会。
