The common ‘Philadelphia chromosome’‐negative myeloproliferative neoplasms (MPN) comprise essential thrombocythaemia, polycythaemia vera and myelofibrosis. These are clinically diverse disorders and present many challenges during their course, ranging from the management of very indolent, chronic‐phase disease through to very aggressive stages frequently associated with poor quality of life, heavy symptom burdens and potentially life expectancies of <18 months. Their management also requires expertise in thrombosis and haemostasis in addition to marrow failure, debilitating symptom control and balancing the ‘pros and cons’ of intensive therapy such as allogeneic stem cell transplant versus novel and established therapies. In the past 15 years this field has seen rapid advances following an understanding of the pivotal importance of constitutive Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling, the interplay of the wider genomic landscape and the development of updated diagnostic criteria, prognostic scores and targeted therapies. In this article, we review the successes and failures of novel agents and approaches to MPN management.

中文翻译：

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前进还是后退：骨髓增生性肿瘤新药的困境和失望

常见的“费城染色体”阴性的骨髓增生性肿瘤（MPN）包括原发性血小板增多症，真性红细胞增多症和骨髓纤维化。这些是临床上多种多样的疾病，并且在其治疗过程中面临许多挑战，范围从轻度的慢性疾病的治疗到非常积极的阶段，这些阶段通常与不良的生活质量，沉重的症状负担以及可能的预期寿命<18个月相关。他们的管理还需要除血栓破裂和止血以外的血栓形成和止血方面的专业知识，使症状控制虚弱并平衡强化治疗（如同种异体干细胞移植与新颖而成熟的疗法。在过去的15年中，随着对组成型Janus激酶/信号转导子和转录激活子（JAK / STAT）信号的关键重要性的理解，更广泛的基因组格局的相互作用以及更新的诊断标准的发展，该领域取得了飞速发展。 ，预后评分和目标疗法。在本文中，我们回顾了新型代理的成功与失败以及MPN管理的方法。