Sangiorgio Valentina, Mottadelli Federica, Pagni Fabio, Cavalca Fabrizio, Cazzaniga Giovanni, Venegoni Martina, Gambacorti-Passerini Carlo, Piazza Rocco, Maria Elli Elena
School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
Tettamanti Center, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy.
Int J Lab Hematol. 2025 Oct;47(5):869-876. doi: 10.1111/ijlh.14476. Epub 2025 Apr 7.
The majority of patients with essential thrombocythemia (ET) show somatic mutations of JAK2, CALR, or MPL. Around 10% of cases lack these mutations ("triple negative" ET, TN-ET). Additionally, some patients with bona fide "primary thrombocytosis" (PT) [i.e., high platelet (PLT)- count with no apparent underlying causes] do not fulfill the histologic criteria of ET. In this context, Next Generation Sequencing (NGS) can provide evidence of clonality and identify patients with different clinical behaviors.
We conducted a retro-prospective analysis of 39 patients with TN-PT and correlated the clinical and pathologic features with the molecular findings.
Bone marrow histopathological features were consistent with ET in 60% of cases. After a mean follow up of 11.1 years, no cases of secondary myelofibrosis nor acute leukemia were observed. We reported 15 thrombotic events (TEs) in 10 (25.6%) patients. Considering mutations with a variant frequency ≥ 5%, 15.4% of patients showed at least one mutation ("NGS-positive"); the remaining had no mutations ("NGS-negative"). NGS status predicted the incidence of TEs: NGS-positive patients experienced a significantly higher rate of TEs compared to NGS-negative patients (66.6% vs. 18.2%, respectively; p = 0.01).
NGS status represents an adjunctive risk factor for thrombosis in TN-PT and provides useful clinical information.
大多数原发性血小板增多症（ET）患者存在JAK2、CALR或MPL的体细胞突变。约10%的病例缺乏这些突变（“三阴性”ET，TN-ET）。此外，一些真正的“原发性血小板增多症”（PT）患者[即血小板（PLT）计数高且无明显潜在病因]不符合ET的组织学标准。在此背景下，二代测序（NGS）可提供克隆性证据并识别具有不同临床行为的患者。
我们对39例TN-PT患者进行了回顾性-前瞻性分析，并将临床和病理特征与分子结果相关联。
60%的病例骨髓组织病理学特征与ET一致。平均随访11.1年后，未观察到继发性骨髓纤维化和急性白血病病例。我们报告了10例（25.6%）患者发生15次血栓形成事件（TEs）。考虑到变异频率≥5%的突变，15.4%的患者至少有一个突变（“NGS阳性”）；其余患者无突变（"NGS阴性"）。NGS状态可预测TEs的发生率：与NGS阴性患者相比，NGS阳性患者的TEs发生率显著更高（分别为66.6%和18.2%；p = 0.01）。
NGS状态代表TN-PT患者血栓形成的一个辅助危险因素，并提供有用的临床信息。
