PDF(Pubmed)
Abstract：
Myeloproliferative neoplasms (MPNs) are hematopoietic diseases characterized by the clonal expansion of single or multiple lineages of differentiated myeloid cells that accumulate in the blood and bone marrow. MPNs are grouped into distinct categories based on key clinical presentations and distinctive mutational hallmarks. These include chronic myeloid leukemia (CML), which is strongly associated with the signature BCR::ABL1 gene translocation, polycythemia vera (PV), essential thrombocythemia (ET), and primary (idiopathic) myelofibrosis (PMF), typically accompanied by molecular alterations in the JAK2, MPL, or CALR genes. There are also rarer forms such as chronic neutrophilic leukemia (CNL), which involves mutations in the CSF3R gene. However, rather than focusing on the differences between these alternate disease categories, this review aims to present a unifying molecular etiology in which these overlapping diseases are best understood as disruptions of normal hematopoietic signaling: specifically, the chronic activation of signaling pathways, particularly involving signal transducer and activator of transcription (STAT) transcription factors, most notably STAT5B, leading to the sustained stimulation of myelopoiesis, which underpins the various disease sequalae.
摘要：
骨髓增殖性肿瘤（MPN）是造血系统疾病，其特征是在血液和骨髓中积累的分化骨髓细胞的单个或多个谱系的克隆扩增。根据关键的临床表现和独特的突变标志，将MPN分为不同的类别。这些包括慢性粒细胞白血病（CML），与签名BCR::ABL1基因易位密切相关，真性红细胞增多症（PV），原发性血小板增多症（ET），和原发性（特发性）骨髓纤维化（PMF），通常伴随着JAK2，MPL，或CALR基因。还有更罕见的形式，如慢性中性粒细胞白血病（CNL），涉及CSF3R基因的突变。然而,而不是关注这些替代疾病类别之间的差异，这篇综述旨在提出一个统一的分子病因，其中这些重叠的疾病被最好地理解为正常造血信号的破坏:信号通路的慢性激活，特别涉及信号转导和转录激活因子（STAT）转录因子，最值得注意的是STAT5B，导致骨髓生成的持续刺激，这是各种疾病后遗症的基础。
