骨髓纤维化的新疗法。

IF 2.3 Q2 HEMATOLOGY Blood Research Pub Date : 2023-04-30 DOI:10.5045/br.2023.2023012
Sung-Eun Lee
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引用次数: 0

摘要

骨髓纤维化(MF)包括原发性MF、原发性血小板增多症MF和真性红细胞增多症MF。MF是一种进行性髓系肿瘤,其特点是克隆造血、髓外造血无效,骨髓环境反应性导致网状蛋白沉积和纤维化,并倾向于白血病转化。JAK2、CALR和MPL驱动突变的鉴定有助于更好地了解疾病的发病机制,并导致了mf特异性治疗的发展,如JAK2抑制剂。尽管ruxolitinib和federatinib已经被临床开发和批准,但由于贫血和血小板减少等不良反应,它们的使用受到限制。最近,pacritinib已被批准用于一组临床需求未得到满足的血小板减少患者。在既往有JAK抑制剂暴露的有症状的贫血患者中,莫美洛替尼在预防贫血加重和控制mf相关体征和症状(如脾脏大小)方面优于达那唑。尽管JAK抑制剂的发展是显著的,但改变疾病的自然过程仍然是一个优先事项。因此,许多新的治疗方法目前正在临床开发中。靶向溴域和外端蛋白、抗凋亡蛋白Bcl-xL和磷脂酰肌醇-3激酶δ的药物已与JAK抑制剂联合研究。这些组合已被用于前线和“附加”方法。此外,一些药物正在研究作为鲁索利替尼耐药或不合格患者的单药治疗。我们回顾了几种处于临床开发晚期的新的MF治疗方法和细胞减少患者的治疗选择。
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Novel therapeutics for myelofibrosis.

Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by ineffective clonal hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity for leukemia transformation. The identification of driver mutations in JAK2, CALR, and MPL has contributed to a better understanding of disease pathogenesis and has led to the development of MF-specific therapies, such as JAK2 inhibitors. Despite the fact that ruxolitinib and fedratinib have been clinically developed and approved, their use is limited due to adverse effects such as anemia and thrombocytopenia. Recently, pacritinib has been approved for a group of thrombocytopenic patients with significant unmet clinical needs. In symptomatic and anemic patients with prior JAK inhibitor exposure, momelotinib was superior to danazol in preventing exacerbation of anemia and in controlling MF-associated signs and symptoms, such as spleen size. Although the development of JAK inhibitors is remarkable, modifying the natural course of the disease remains a priority. Therefore, many novel treatments are currently under clinical development. Agents targeting bromodomain and extra-terminal protein, anti-apoptotic protein Bcl-xL, and phosphatidylinositol-3-kinase delta have been studied in combination with JAK inhibitors. These combinations have been employed in both the frontline and "add-on" approaches. In addition, several agents are being studied as monotherapies for ruxolitinib-resistant or -ineligible patients. We reviewed several new MF treatments in the advanced stages of clinical development and treatment options for cytopenic patients.

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来源期刊
Blood Research
Blood Research HEMATOLOGY-
CiteScore
3.70
自引率
0.00%
发文量
64
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