Division of Hematology, Department of Internal Medicine, Faculty of Medicine, İstanbul University, İstanbul, Turkey.
Division of Hematology, Department of Internal Medicine, Hamidiye Faculty of Medicine, University of Health Sciences, İstanbul, Turkey.
Turk J Med Sci. 2022 Feb;52(1):150-165. doi: 10.3906/sag-2103-247. Epub 2022 Feb 22.
JAK2V617F mutation is expressed in almost all polycthemia vera (PV), 55% of essential thrombocythemia (ET), and 65% of primary myelofibrosis (PMF) patients. Studies investigating phenotypic effects of JAK2V617F mutation on Philadelphianegative myeloproliferative neoplasms (Ph-negative MPNs) have reported controversial results. This study aims to determine the impact of JAK2V617F mutation on clinical phenotype and outcome in Ph-negative MPNs.
Clinical correlates and long-term prognostic relevance of the JAK2V617F mutation were analyzed in 410 Phnegative MPNs-170 ET, 135 PV, 105 PMF- from two institutions and followed for a mean of 76.7 months (SD 62.1) (mean 87 months (SD 67.8), 70.4 months (SD 56.4), 68 months (SD 57.4), respectively for ET, PV, and PMF). Two hundred and twenty-eight patients were genotyped for JAK2V617F mutation using the JAK2 Ipsogen MutaScreen assay, which involves allele-specific polymerase chain reaction (PCR), and 182 patients were genotyped using melting curve analysis.
In PV patients, JAK2V617F mutation was associated with higher rate in females, lower hemoglobin (Hgb) level, higher leukocyte and platelet count and higher prevalence of thrombosis (p = 0.008, p = 0.018, p = 0.001, p = 0.001, and p = 0.035, respectively). In ET patients, JAK2V617F mutation was associated with higher Hgb and hematocrit (Hct) levels and lower platelet count (p = 0.001, p = 0.001, and p = 0.001, respectively). JAK2V617F-negative ET patients showed a trend towards higher rate of leukemic transformation (p = 0.061). JAK2V617F mutation-positive PMF patients had higher leukocyte count, greater spleen size and showed a trend towards higher Hgb level (p = 0.019, p = 0.042, and p = 0.056, respectively). Among PMF patients with JAK2V617F mutation, the rate of female patients was lower (p = 0.001). Overall survival (OS) in Dynamic International Prognostic Scoring System (DIPSS) - plus high risk PMF patients was shorter compared to the other risk groups (p = 0.001). Leukemia-free survival (LFS) was shorter in DIPSS - plus high risk PMF patients than the other risk groups (p = 0.005). In the entire cohort of Ph-negative MPN patients, JAK2V617F mutation was associated with higher leukocyte count, higher Hgb and Hct levels and lower platelet count, higher frequency of phlebotomies, a trend towards older age, a trend towards greater spleen size, a trend towards a higher prevalence of risk factors for cardiovascular diseases and thrombosis (p = 0.001, p = 0.005, p = 0.001, p = 0.003, p = 0.004, p =0.052, p = 0.056, p = 0.052, and p = 0.059, respectively).
JAK2V617F 突变几乎存在于所有真性红细胞增多症（PV）、55%的原发性血小板增多症（ET）和 65%的原发性骨髓纤维化（PMF）患者中。研究表明 JAK2V617F 突变对费城阴性骨髓增殖性肿瘤（Ph-阴性 MPNs）的表型效应存在争议。本研究旨在确定 JAK2V617F 突变对 Ph-阴性 MPNs 临床表型和结局的影响。
对来自两个机构的 410 例 Ph-阴性 MPNs（170 例 ET、135 例 PV、105 例 PMF）进行 JAK2V617F 突变的临床相关性和长期预后相关性分析，中位随访时间为 76.7 个月（62.1）（分别为 87 个月（67.8）、70.4 个月（56.4）和 68 个月（57.4），用于 ET、PV 和 PMF）。228 例患者采用 JAK2 Ipsogen MutaScreen 检测试剂盒进行 JAK2V617F 突变基因分型，该试剂盒涉及等位基因特异性聚合酶链反应（PCR），182 例患者采用熔解曲线分析进行基因分型。
在 PV 患者中，JAK2V617F 突变与女性比例较高、较低的血红蛋白（Hgb）水平、较高的白细胞和血小板计数以及较高的血栓形成发生率相关（p=0.008、p=0.018、p=0.001、p=0.001 和 p=0.035，分别）。在 ET 患者中，JAK2V617F 突变与较高的 Hgb 和血细胞比容（Hct）水平以及较低的血小板计数相关（p=0.001、p=0.001 和 p=0.001，分别）。JAK2V617F 阴性 ET 患者白血病转化率较高（p=0.061）。JAK2V617F 阳性 PMF 患者白细胞计数较高，脾脏较大，且 Hgb 水平呈升高趋势（p=0.019、p=0.042 和 p=0.056，分别）。在 JAK2V617F 阳性 PMF 患者中，女性患者比例较低（p=0.001）。与其他风险组相比，动态国际预后评分系统（DIPSS）加高危 PMF 患者的总生存率（OS）更短（p=0.001）。DIPSS 加高危 PMF 患者的无白血病生存率（LFS）较其他风险组更短（p=0.005）。在整个 Ph-阴性 MPN 患者队列中，JAK2V617F 突变与较高的白细胞计数、较高的 Hgb 和 Hct 水平以及较低的血小板计数、较高的放血频率、年龄较大、脾脏较大、心血管疾病和血栓形成风险因素的发生率较高相关（p=0.001、p=0.005、p=0.001、p=0.003、p=0.004、p=0.052、p=0.056、p=0.052 和 p=0.059，分别）。
