Myelofibrosis (MF) is a clonal myeloproliferative neoplasm (MPN) characterized clinically by cytopenias, fatigue, and splenomegaly stemming from extramedullary hematopoiesis. MF commonly arises from mutations inJAK2,MPL, andCALR, which manifests as hyperactive Jak/Stat signaling. Triple-negative MF is diagnosed in the absence ofJAK2,MPL, andCALRbut when clinical, morphologic criteria are met and other mutation(s) is/are present, includingASXL1,EZH2, andSRSF2. While the clinical and classic molecular features of MF are well-established, emerging evidence indicates that additional mutations, specifically within the Ras/MAP Kinase signaling pathway, are present and may play important role in disease pathogenesis and treatment response.KRASandNRASmutations alone are reportedly present in up to 15 and 14% of patients with MF (respectively), and other mutations predicted to activate Ras signaling, such asCBL,NF1,BRAF, andPTPN11, collectively exist in as much as 21% of patients. Investigations into the prevalence ofRASand related pathway mutations in MF and the mechanisms by which they contribute to its pathogenesis are critical in better understanding this condition and ultimately in the identification of novel therapeutic targets.
骨髓纤维化（MF）是一种克隆性骨髓增殖性肿瘤（MPN），其临床特征表现为血细胞减少、疲劳以及由髓外造血引起的脾肿大。MF通常由JAK2、MPL和CALR基因突变引发，表现为Jak/Stat信号通路过度激活。当患者缺乏JAK2、MPL和CALR突变但符合临床及形态学诊断标准，且存在其他基因突变（如ASXL1、EZH2、SRSF2等）时，可诊断为三阴性MF。尽管MF的临床及经典分子特征已较为明确，但新近证据表明，其他突变——特别是Ras/MAP激酶信号通路内的突变——在MF中普遍存在，并可能在疾病发病机制及治疗反应中发挥重要作用。据报道，仅KRAS和NRAS突变在MF患者中的发生率分别高达15%和14%，而其他可激活Ras信号通路的突变（如CBL、NF1、BRAF、PTPN11）总体存在于高达21%的患者中。深入研究RAS及相关通路突变在MF中的流行情况及其促进疾病发生的机制，对于更深入理解该疾病并最终确定新的治疗靶点至关重要。
肿瘤(癌症)患者之家