Ling Victoria Y, Heidel Florian H, Bywater Megan J
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Department of Haematology, Princess Alexandra Hospital, Brisbane, Queensland, Australia; Pathology Queensland, Brisbane, Queensland, Australia; The University of Queensland, Brisbane, QLD.
Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany; Leibniz Institute on Aging, Jena, Germany; Cellular Therapy Center (CTC), Hannover Medical School (MHH), Hannover.
Haematologica. 2025 Apr 1;110(4):863-876. doi: 10.3324/haematol.2023.283987. Epub 2024 Dec 5.
Classical myeloproliferative neoplasms (MPN) are clonal stem cell disorders characterized by driver mutations that affect the constitutive activation of JAK-signaling. Mutations additional to an MPN-driver occur in a large number of patients and have been shown be associated with disease presentation and progression. In this review, we outline the current hypotheses regarding how clonal evolution in MPN is thought to occur and the functional mechanisms as to how concomitant somatic mutations (i.e., mutations in genes other than the 'driver' genes) contribute to disease progression. We discuss the definitions of high molecular risk MPN, provide an overview of how concomitant mutations influence the clinical management of MPN and suggest how the rapidly developing genetic risk stratification can be utilized to improve clinical outcomes.
经典型骨髓增殖性肿瘤（MPN）是一类克隆性干细胞疾病，其特征是驱动突变影响JAK信号的组成性激活。大量MPN患者除了存在MPN驱动突变外，还发生了其他突变，这些突变已被证明与疾病的表现和进展有关。在本综述中，我们概述了目前关于MPN克隆进化如何发生的假说，以及伴随的体细胞突变（即“驱动”基因以外的基因中的突变）如何促进疾病进展的功能机制。我们讨论了高危MPN的定义，概述了伴随突变如何影响MPN的临床管理，并提出如何利用快速发展的遗传风险分层来改善临床结果。
