Department of Biomedicine, University Hospital Basel and University of Basel, Hebelstrasse 20, Basel CH-4031, Switzerland.
Department of Biomedicine, University Hospital Basel and University of Basel, Hebelstrasse 20, Basel CH-4031, Switzerland; Division of Hematology, University Hospital Basel, Petersgraben 4, Basel CH-4031, Switzerland.
Hematol Oncol Clin North Am. 2021 Apr;35(2):217-236. doi: 10.1016/j.hoc.2020.12.002. Epub 2021 Jan 29.
Myeloproliferative neoplasms are hematopoietic stem cell disorders based on somatic mutations in JAK2, calreticulin, or MPL activating JAK-STAT signaling. Modern sequencing efforts have revealed the genomic landscape of myeloproliferative neoplasms with additional genetic alterations mainly in epigenetic modifiers and splicing factors. High molecular risk mutations with adverse outcomes have been identified and clonal evolution may promote progression to fibrosis and acute myeloid leukemia. JAK2V617F is recurrently detected in clonal hematopoiesis of indeterminate potential with increased risk for vascular events. Insights into the genetics of myeloproliferative neoplasms has facilitated diagnosis and prognostication and poses novel candidates for targeted therapeutic intervention.
骨髓增殖性肿瘤是基于 JAK2、钙网蛋白或 MPL 体细胞突变导致 JAK-STAT 信号激活的造血干细胞疾病。现代测序工作揭示了骨髓增殖性肿瘤的基因组景观，其中还存在主要为表观遗传修饰因子和剪接因子的其他遗传改变。已经确定了具有不良结局的高分子风险突变，克隆进化可能会促进纤维化和急性髓系白血病的进展。JAK2V617F 在具有血管事件风险增加的不确定潜能的克隆性造血中经常被检测到。对骨髓增殖性肿瘤遗传学的深入了解促进了诊断和预后，并为靶向治疗干预提供了新的候选靶点。
