Inserm U1231, Université de Bourgogne, 21000 Dijon, France.
Institut IMAGINE, Inserm U1163, 75015 Paris, France.
Genes (Basel). 2022 Apr 2;13(4):637. doi: 10.3390/genes13040637.
Polycythemia vera belongs to myeloproliferative neoplasms, essentially by affecting the erythroblastic lineage. JAK2 alterations have emerged as major driver mutations triggering PV-phenotype with the mutation detected in nearly 98% of cases. That's why JAK2 targeting therapeutic strategies have rapidly emerged to counter the aggravation of the disease. Over decades of research, to go further in the understanding of the disease and its evolution, a wide panel of genetic alterations affecting multiple genes has been highlighted. These are mainly involved in alternative splicing, epigenetic, miRNA regulation, intracellular signaling, and transcription factors expression. If JAK2 mutation, irrespective of the nature of the alteration, is known to be a crucial event for the disease to initiate, additional mutations seem to be markers of progression and poor prognosis. These discoveries have helped to characterize the complex genomic landscape of PV, resulting in potentially new adapted therapeutic strategies for patients concerning all the genetic interferences.
真性红细胞增多症属于骨髓增殖性肿瘤，主要通过影响红系前体细胞。JAK2 改变已成为触发 PV 表型的主要驱动突变，约 98%的病例中均可检测到该突变。这就是为什么 JAK2 靶向治疗策略迅速出现，以对抗疾病的恶化。经过几十年的研究，为了更深入地了解疾病及其演变，人们强调了一组影响多个基因的广泛遗传改变。这些改变主要涉及可变剪接、表观遗传、miRNA 调控、细胞内信号转导和转录因子表达。如果 JAK2 突变，无论其改变的性质如何，都被认为是疾病发生的关键事件，那么其他突变似乎是疾病进展和预后不良的标志物。这些发现有助于描述 PV 的复杂基因组景观，为所有遗传干扰的患者制定潜在的新的适应性治疗策略。
