Kvasnicka Hans Michael
Institute of Pathology and Department of Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke.
Rinsho Ketsueki. 2019;60(9):1166-1175. doi: 10.11406/rinketsu.60.1166.
The classical myeloproliferative neoplasms (MPN), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by clonal myeloproliferation without features of myelodysplasia. The diagnostic approach proposed by the World Health Organization (WHO) uses clinical features, peripheral blood counts and smear analysis, bone marrow (BM) morphology, karyotype and molecular genetic tests to classify MPN subtypes. The detection of characteristic driver mutations like JAK2V617F, JAK2 exon 12, MPL, and calrecticulin (CALR) is a major diagnostic feature. JAK2 mutations are detected in more than 90% of patients with PV and are therefore used as highly sensitive clonal marker in this subtype. However, JAK2 mutations may also occur in ET and PMF, while CALR is virtually not seen in PV. Therefore, BM remains the central diagnostic platform and is essential for distinguishing ET from pre-fibrotic PMF and diagnosing cases which do not express JAK2, MPL or CALR ('wild-type' or 'triple-negative' MPN). The standardization of relevant BM features is mandatory to recognize characteristic and easy to assess patterns that enable an accurate discrimination between the MPN subtypes. Key parameters include cellularity, erythropoiesis and neutrophil granulopoiesis in context with specific features of megakaryocytes as well as the BM fiber content, especially in early stage MPN that present with thrombocytosis and clinically mimic essential thrombocythemia.
经典型骨髓增殖性肿瘤（MPN），包括真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF），其特征为克隆性骨髓增殖，无骨髓发育异常特征。世界卫生组织（WHO）提出的诊断方法利用临床特征、外周血细胞计数及涂片分析、骨髓（BM）形态学、核型和分子遗传学检测来对MPN亚型进行分类。检测特征性驱动突变如JAK2V617F、JAK2第12外显子、MPL和钙网蛋白（CALR）是主要的诊断特征。超过90%的PV患者可检测到JAK2突变，因此在该亚型中用作高度敏感的克隆标志物。然而，JAK2突变也可能出现在ET和PMF中，而PV中几乎不见CALR突变。因此，骨髓仍然是核心诊断平台，对于区分ET与纤维化前PMF以及诊断不表达JAK2、MPL或CALR的病例（“野生型”或“三阴性”MPN）至关重要。相关骨髓特征的标准化对于识别特征性且易于评估的模式以准确区分MPN亚型是必不可少的。关键参数包括细胞成分、红细胞生成和中性粒细胞生成以及巨核细胞的特定特征，还有骨髓纤维含量，尤其是在表现为血小板增多症且临床上酷似原发性血小板增多症的早期MPN中。
