Department of Internal Medicine III, University of Ulm, Germany.
Curr Cancer Drug Targets. 2011 Jan;11(1):72-84. doi: 10.2174/156800911793743682.
The four major entities that form the group of myeloproliferative neoplasms (MPN) are BCR-ABL positive chronic myeloid leukaemia (CML), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET) and polycythemia vera (PV). All four are clonal diseases of the haematopoietic stem or precursor cell, they are of a chronic nature and potentially aggravate to myelofibrosis or transform into acute leukaemia. Several strategies are pursued in the treatment of MPN. On the one hand, targeted therapies such as tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) and JAK2-inhibitors are adopted in MPN as well as rather unspecific treatment with interferon-alpha and with the newer group of immunomodulatory drugs (IMIDs). On the other hand, cellular immunotherapeutical options as allogeneic haematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI) are exerted in patients with MPN. Evidence resulting from graft-versus-leukaemia (GvL) effect was the key to develop more specific immunotherapies for patients with haematologic malignancies. In this context, CML is a model for immunotherapeutic approaches, and therefore, vaccination trials using peptides derived from leukaemia-associated antigens (LAAs) to stimulate specific T cells are currently under investigation. But also in BCR-ABL-negative MPNs, antigens have been identified and immunomodulatory treatment strategies have been performed. All of the current immunotherapeutical options in patients with MPN will be discussed throughout this review.
形成骨髓增殖性肿瘤（MPN）组的四个主要实体是 BCR-ABL 阳性慢性髓性白血病（CML）、特发性慢性骨髓纤维化（CIMF）、原发性血小板增多症（ET）和真性红细胞增多症（PV）。这四种疾病均为造血干细胞或前体细胞的克隆性疾病，它们具有慢性性质，并且可能恶化至骨髓纤维化或转化为急性白血病。在 MPN 的治疗中，采用了几种策略。一方面，针对 MPN 采用了靶向治疗，如酪氨酸激酶抑制剂（伊马替尼、达沙替尼、尼洛替尼）和 JAK2 抑制剂，以及干扰素-α和较新的免疫调节药物（IMIDs）等非特异性治疗。另一方面，在 MPN 患者中，采用了细胞免疫治疗选择，如异基因造血干细胞移植（HSCT）和供体淋巴细胞输注（DLI）。移植物抗白血病（GvL）效应的证据是为血液恶性肿瘤患者开发更特异免疫治疗的关键。在这方面，CML 是免疫治疗方法的模型，因此，目前正在研究使用源自白血病相关抗原（LAAs）的肽来刺激特异性 T 细胞的疫苗试验。但在 BCR-ABL 阴性 MPN 中，也已经鉴定了抗原，并进行了免疫调节治疗策略。本综述将讨论 MPN 患者的所有当前免疫治疗选择。
