aDepartment of Translational Hematology and Oncology Research bCleveland Clinic Taussig Cancer Institute cLeukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA *Both authors contributed equally to the writing of this article.
Curr Opin Hematol. 2014 Mar;21(2):131-40. doi: 10.1097/MOH.0000000000000021.
Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), including chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN-Unclassifiable, ring sideroblasts associated with marked thrombocytosis, and juvenile myelomonocytic leukemia, are clonal hematologic diseases characterized by myeloid dysplasia, proliferation, and absence of the molecular lesions BCR/ABL, PDGFRA, PDGFRB, and FGFR1. There are currently no US Food and Drug Administration approved therapies for all MDS/MPN subtypes. Advances in the understanding of the biologic and molecular drivers of these diseases will help in diagnosis, prognosis, and therapeutics. This review article summarizes the molecular aspects of MDS/MPNs and provides an overview of classic and emerging therapies.
Next generation sequencing has provided new insights into the genetic nature of MDS/MPNs. Molecular mutations such as TET2, CBL, SETBP1, CSF3R, and SF3B1 are relevant as diagnostic and prognostic biomarkers. Hematopoietic cell transplantation, although potentially curative, is applicable to only a small proportion of patients. Attempts to standardize response and outcomes criteria specific to MDS/MPN and clinical trials using novel agents focused on MDS/MPN patients are underway.
MDS/MPNs have clinicopathologic features of both MDS and MPN diseases. Emerging molecular data support the distinctive disease biology of each of these morphologic entities, and will serve as the foundation to develop effective therapeutics that can ameliorate disease-related complications and lead to better outcomes.
骨髓增生异常/骨髓增殖性肿瘤（MDS/MPN），包括慢性粒单核细胞白血病、不典型慢性髓系白血病、不能分类的 MDS/MPN、环形铁幼粒细胞伴显著血小板增多症和青少年粒单核细胞白血病，是一类以髓系增生、发育异常和缺乏 BCR/ABL、PDGFRA、PDGFRB 和 FGFR1 等分子病变为特征的克隆性血液病。目前，尚无美国食品和药物管理局批准的治疗所有 MDS/MPN 亚型的药物。对这些疾病的生物学和分子驱动因素的认识的进步将有助于诊断、预后和治疗。本文综述了 MDS/MPN 的分子特征，并概述了经典和新兴的治疗方法。
下一代测序为 MDS/MPN 的遗传性质提供了新的认识。TET2、CBL、SETBP1、CSF3R 和 SF3B1 等分子突变可作为诊断和预后生物标志物。造血细胞移植虽然有治愈的可能，但仅适用于一小部分患者。目前正在努力制定针对 MDS/MPN 的标准化反应和结局标准，并开展针对 MDS/MPN 患者的新型药物临床试验。
MDS/MPN 具有 MDS 和 MPN 疾病的临床病理特征。新兴的分子数据支持这些形态实体中每一种疾病独特的生物学特性，这将成为开发有效治疗方法的基础，这些方法可以改善与疾病相关的并发症，并带来更好的结果。
