Blood. 2014 Dec 4;124(24):3529-37. doi: 10.1182/blood-2014-05-577635.
Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression( pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.
骨髓增殖性肿瘤，包括真性红细胞增多症（PV）、原发性血小板增多症和骨髓纤维化（MF）（原发性和继发性），其特征是症状严重、有生命危险的并发症，且有进展为急性白血病的风险。近年来，我们在诊断和预后这些克隆性恶性肿瘤方面的能力不断提高，同时也开发了针对 MPN 的靶向治疗方法，这些方法显著改善了疾病负担和生活质量。芦可替尼在缓解 MF 患者的症状负担、减少脾肿大和改善生活质量方面取得了成功。JAK 抑制的作用和临床预期继续扩展到各种研究领域。MF 患者的临床试验重点是新的 JAK 抑制剂，这些抑制剂可能具有较少的骨髓抑制作用（pacritinib），甚至对贫血有活性（momelotinib）。进一步的努力集中在联合试验（包括 JAK 抑制剂基础）或针对新途径（例如端粒酶）。同样，PV 的治疗也在不断发展，第 3 阶段试验正在研究一线治疗（羟基脲或 IFN）的最佳方案，以及 JAK 抑制剂治疗羟基脲耐药或不耐受的 PV 的二线治疗。在这一章中，我们回顾了 JAK 抑制（单独或联合使用）在 MPN 患者管理中的不断发展的数据和作用。
