Department of Hematology, Copenhagen University Hospital, Roskilde Hospital, Roskilde, Denmark.
Curr Drug Targets. 2011 Mar 1;12(3):392-419. doi: 10.2174/138945011794815275.
The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F mutation in the large majority of patients with PV and in half of those with ET and PMF. A number of studies have shown that the "tumor burden" may be monitored at the molecular level in JAK2-positive patients using highly sensitive real-time quantitative PCR. During the last 25 years several studies have shown that interferon-alpha (IFN-alpha) induces complete haematological remissions in a large proportion of the patients. However, its use in clinical practice has unfortunately been limited due to side effects with high drop-out rates in most studies. Recently, IFN-alpha2 has been shown to induce deep molecular remissions and also normalization of the bone marrow in PV, which may be sustained even after discontinuation of IFN-alpha2 therapy. Accordingly, in the coming years we are most likely facing a new era of increasing interest for using IFN-alpha2 in the treatment of patients with PV, ET and the hyperproliferative phase of PMF. This paper reviews the history of IFN - in principle IFN-alpha2 - and its present status in the treatment of PV and related diseases. The role of IFN-alpha2 as immune therapy in the future treatment of CMPNs is highlighted and the rationale for the concept of minimal residual disease and potentially cure after long-term immune therapy with IFN-alpha2 is discussed and foreseen as an achievable goal in the future.
费城阴性慢性骨髓增殖性肿瘤包括原发性血小板增多症（ET）、真性红细胞增多症（PV）和原发性骨髓纤维化（PMF）。2005 年，人们发现大多数 PV 患者和约一半的 ET 和 PMF 患者存在 JAK2 V617F 突变，这一发现极大地促进了人们对这些肿瘤发病机制的理解。许多研究表明，在 JAK2 阳性患者中，可以使用高度敏感的实时定量 PCR 在分子水平监测“肿瘤负担”。在过去的 25 年中，有几项研究表明，干扰素-α（IFN-α）可诱导很大一部分患者完全血液学缓解。然而，由于副作用较大，大多数研究中的脱落率较高，其在临床实践中的应用受到限制。最近，IFN-α2 已被证明可诱导 PV 患者的深度分子缓解和骨髓正常化，即使在停止 IFN-α2 治疗后，这种缓解也可能持续存在。因此，在未来几年，我们很可能面临一个新的时代，越来越多的人对使用 IFN-α2 治疗 PV、ET 和 PMF 的增殖期感兴趣。本文回顾了 IFN-α的历史——原则上是 IFN-α2——及其在 PV 和相关疾病治疗中的现状。强调了 IFN-α2 作为免疫疗法在未来 CMPNs 治疗中的作用，并讨论了微小残留疾病概念的合理性以及长期 IFN-α2 免疫治疗后可能治愈的前景，认为这是未来可以实现的目标。
