Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland.
Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
J Cancer Res Clin Oncol. 2023 Jul;149(8):4789-4803. doi: 10.1007/s00432-022-04327-0. Epub 2022 Oct 15.
Despite comparatively favourable prognosis in polycythemia vera (PV) patients (pts), the overall survival is shorter compared to the age-matched general population. The aim of the study was to evaluate the impact of chosen laboratory and genetic factors on the individual disease outcome, i.e. risk of thrombosis, myelofibrosis/blastic transformation and death.
The study group consisted of 151 pts and 57 healthy donors (HD).
JAK2V617F mutation was found in 96.7% (146/151) of the studied pts. JAK2 exon 12 mutations were identified in 2 individuals. The coexistence of JAK2V617F and JAK2 exon 12 mutation was confirmed in 2 other pts. In one case, neither JAK2V617F nor JAK2 exon 12 mutation was found. The presence of ten different non-driver mutations (ASXL1, SRSF2, U2AF1, IDH2) in eight of the analyzed pts (5.3%) was confirmed. The overall frequency of thrombotic events (TE) in the studied PV group was 23.8% (36/151). In patients with TE, median platelet count was lower than in pts without TE. Thrombotic risk did not depend on JAK2 rs12343867, TERT rs2736100, OBFC1 rs9420907 SNV, however, we found a novel strong tendency towards statistical significance between the CC genotype miR-146a rs2431697 and thrombosis. The disease progression to fibrotic phase was confirmed in 9% of the pts. Fibrotic transformation in PV pts was affected mainly by JAK2V617F variant allele frequency (VAF) and the presence of coexisting non-driver variants. The high JAK2V617F VAF and elevated white blood cell (WBC) count at the time of diagnosis were associated with an increased risk of death.
Therefore, in our opinion, complex, laboratory and genetic PV pts evaluation at the time of diagnosis should be incorporated into a new prognostic scoring system to more precisely define the PV prognosis and to optimize the therapeutic decision-making process.
尽管原发性骨髓纤维化（PV）患者的预后相对较好，但与年龄匹配的一般人群相比，其总体生存率仍较低。本研究的目的是评估所选实验室和遗传因素对个体疾病结局的影响，即血栓形成、骨髓纤维化/原始细胞转化和死亡的风险。
研究组包括 151 名患者和 57 名健康供体（HD）。
在 151 名研究患者中发现 JAK2V617F 突变 96.7%（146/151）。在 2 名患者中鉴定出 JAK2 外显子 12 突变。在另外 2 名患者中证实存在 JAK2V617F 和 JAK2 外显子 12 突变的共存。在 1 例中，既未发现 JAK2V617F 也未发现 JAK2 外显子 12 突变。在分析的 8 名患者（5.3%）中证实存在 10 种不同的非驱动突变（ASXL1、SRSF2、U2AF1、IDH2）。在研究的 PV 组中，总血栓形成事件（TE）的发生率为 23.8%（36/151）。在发生 TE 的患者中，血小板计数中位数低于未发生 TE 的患者。血栓形成风险与 JAK2 rs12343867、TERT rs2736100、OBFC1 rs9420907 SNV 无关，但我们发现 miR-146a rs2431697 的 CC 基因型与血栓形成之间存在强烈的统计学趋势。在 9%的患者中证实疾病进展为纤维化期。PV 患者的纤维化转化主要受 JAK2V617F 变体等位基因频率（VAF）和共存非驱动变异体的影响。高 JAK2V617F VAF 和诊断时白细胞计数升高与死亡风险增加相关。
因此，我们认为，在诊断时对 PV 患者进行复杂的实验室和遗传评估应纳入新的预后评分系统，以更准确地定义 PV 预后并优化治疗决策过程。
