新时代的骨髓纤维化治疗: 超越Janus激酶抑制剂单一疗法 - 注重BCL-XL/BCL-2抑制剂navitoclax的临床发展
New era for myelofibrosis treatment with novel agents beyond Janus kinase-inhibitor monotherapy: Focus on clinical development of BCL-XL /BCL-2 inhibition with navitoclax.
发表日期：2023 Aug 16
作者：
Naveen Pemmaraju, Jacqueline S Garcia, Andrew Perkins, Jason G Harb, Andrew J Souers, Michael E Werner, Christopher M Brown, Francesco Passamonti
来源：
CANCER
摘要：
骨髓纤维化是一种异质性的造血增生性肿瘤，表现为慢性炎症、进行性骨髓衰竭和肝脾外骨髓造血。类似Janus激酶抑制剂单药（如瑞诺替尼）的治疗可显著减轻脾脏肿大和症状，但对于持久的疾病修正能力有限。迫切需要一种新机制的治疗方法，能够修改潜在的病理生理学，并改变骨髓纤维化的疾病进程。本综述重点介绍了B细胞淋巴瘤（BCL）蛋白BCL-extra large（BCL-XL）在疾病发病机制中的作用，以及BCL-extra large/BCL-2抑制剂纳维拓可斯（navitoclax）在骨髓纤维化治疗中的潜在作用。© 2023美国癌症协会。
Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-XL ) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment.© 2023 American Cancer Society.