Myeloproliferative neoplasms (MPNs) are a set of chronic hematopoietic neoplasms with overlapping clinical and molecular features. Recent years have witnessed considerable advances in our understanding of their pathogenetic basis. Due to their protracted clinical course, the evolution to advanced hematological malignancies, and the accessibility of neoplastic tissue, the study of MPNs has provided a window into the earliest stages of tumorigenesis. With the discovery of mutations in CALR, the majority of MPN patients now bear an identifiable marker of clonal disease; however, the mechanism by which mutated CALR perturbs megakaryopoiesis is currently unresolved. We are beginning to understand better the role of JAK2(V617F) homozygosity, the function of comutations in epigenetic regulators and spliceosome components, and how these mutations cooperate with JAK2(V617F) to modulate MPN phenotype.

中文翻译：

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骨髓增生性疾病的发病机制。

骨髓增生性肿瘤 (MPN) 是一组具有重叠临床和分子特征的慢性造血肿瘤。近年来，我们对其发病机制的理解取得了相当大的进展。由于其漫长的临床过程、向晚期血液系统恶性肿瘤的演变以及肿瘤组织的可及性，MPN 的研究为了解肿瘤发生的早期阶段提供了一个窗口。随着 CALR 突变的发现，大多数 MPN 患者现在都带有可识别的克隆性疾病标志物。然而，突变的 CALR 扰乱巨核细胞生成的机制目前尚未解决。我们开始更好地理解 JAK2（V617F）纯合性的作用，表观遗传调节因子和剪接体成分中的交换功能，