台灣原發性血小板增多症患者基因特徵

Genetic characteristics of essential thrombocythemia patients in Taiwan

原發性血小板增多症（essential thrombocythemia, ET）是一種骨髓增生性腫瘤（Myeloproliferative neoplasms, MPN），原發性血小板增多症的主要分子致病機轉為JAK2、CALR或是MPL基因突變導致造血細胞過度生成。雖然形態學和臨床實驗室分析在定義MPN方面發揮重要依據，然而2016年世界衛生組織（WHO）己將JAK2、MPL和CALR突變作為診斷標準之一，因此我們收集台灣157位原發性血小板增多症患者進行其基因與其相關臨床分析，結果顯示JAK2 V617F占69%；CALR突變占14%；MPL突變占7%；三個基因突變都為陰性者則占10%。JAK2 V617F ET患者的周邊血白血球（WBC）計數較其他基因突變患者高; CALR突變患者之血小板計數明顯高於其他基因突變患者; MPL突變血色素相對其他基因低。收集的原發性血小板增多症患者中，女性所占比例明顯高於男性，尤其是CALR及MPL基因的變異。另外重要的是我們發現原發性血小板增多症病人JAK2 V617F的VAF（variant allele frequency）中位數只有18.59%，這個發現可與其他臨床表现结合起來，作為與其他兩型骨髓增生性腫瘤區分的参考。

Essential thrombocythemia (ET) is one of the myeloproliferative neoplasms. The primary cause of essential thrombocythemia is the overproduction of hematopoietic cells due to mutations in the JAK2, CALR, or MPL genes. Although morphology and clinical laboratory analysis continue to play an important role in defining these conditions, emphasis on molecular testing in MPN is made by the World Health Organization by including JAK2, MPL, and CALR mutations as one of the diagnostic criteria in the 2016 update on the classification of myeloid neoplasms. Therefore, we collected 157 patients with essential thrombocythemia in Taiwan to perform genetic and relevant clinical data analyses. Our results showed that the JAK2 V617F mutation was found in 69% of the patients, the CALR mutation in 14%, the MPL mutation in 7%, and triple-negative mutations in 10% of our ET cohort. The white blood cells (WBC) of JAK2 p.V617F are higher than those of other gene mutations; essential thrombocythemia (ET) patients with CALR mutations had significantly higher platelet counts. Patients with essential thrombocythemia (ET) who have mutations in MPL exhibit low hemoglobin (Hb). Among the patients diagnosed with essential thrombocythemia, the proportion of women is significantly higher than that of men, particularly about mutations in the CALR and MPL genes. Another important finding is that the median variant allele frequency (VAF) of JAK2 V617F in patients with essential thrombocythemia is only 18.59%. This information may be used, in conjunction with other clinical manifestations, as a reference to distinguish it from the other two types of myeloproliferative neoplasms.