Segura-Díaz Adrián, Stuckey Ruth, Florido Yanira, González-Martín Jesús María, López-Rodríguez Juan Francisco, Sánchez-Sosa Santiago, González-Pérez Elena, Sáez Perdomo María Nieves, Perera María Del Mar, de la Iglesia Silvia, Molero-Labarta Teresa, Gómez-Casares María Teresa, Bilbao-Sieyro Cristina
Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain.
Investigation Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain.
Cancers (Basel). 2020 Apr 10;12(4):934. doi: 10.3390/cancers12040934.
The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in and (DTA genes) was positively associated with age for the whole cohort ( = 0.025, OR: 1.047, 95% CI: 1.006-1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients ( = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of ≥1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, = 0.0024). Specifically, mutations in were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95% CI: 1.15-11.83, = 0.031). Our results suggest that pathogenic DTA mutations, and particularly mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort.
血栓形成事件在真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者中很常见。我们使用二代测序（NGS）研究了在68例骨髓增殖性肿瘤（MPN）患者的初始队列中，与髓系恶性肿瘤频繁相关的致病突变对血栓形成事件的影响。正如预期的那样，整个队列中 和 （DTA基因）的突变与年龄呈正相关（ = 0.025，OR：1.047，95%CI：1.006 - 1.090）。此外，虽然DTA突变与整个队列中的事件无关，但在PV患者中，DTA突变与血管事件的发生密切相关（ = 0.028）。为了证实DTA突变的存在与血栓形成事件之间可能的关联，我们对55例年龄匹配的PV患者进行了病例对照研究（包括初始队列中的12例PV患者，25例有事件患者与30例无事件患者）。在年龄匹配的PV病例对照队列中，≥1个DTA突变的存在显著增加了血栓形成事件的风险（OR：6.333， = 0.0024）。具体而言，在PV病例对照队列中， 的突变与血栓形成事件相关（OR：3.56，95%CI：1.15 - 11.83， = 0.031）。我们的结果表明，致病的DTA突变，特别是 突变，可能是PV患者血栓形成的独立危险因素。然而， 和DTA突变在ET和PMF中的预测价值尚无定论，应在更大的队列中确定。
