Kang Min-Gu, Choi Hyun-Woo, Lee Jun Hyung, Choi Yong Jun, Choi Hyun-Jung, Shin Jong-Hee, Suh Soon-Pal, Szardenings Michael, Kim Hye-Ran, Shin Myung-Geun
Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea.
Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, South Korea.
Oncotarget. 2016 Aug 30;7(35):57036-57049. doi: 10.18632/oncotarget.10958.
Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%) of 167 ET patients. Clinical characteristics, progression-free survival (PFS), and elapsed time to achieve partial remission across 4 groups (JAK2+/CALR+, JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR-) were reviewed. The JAK2+/CALR- group had higher leukocyte counts and hemoglobin levels and more frequent thrombotic events than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease phenotype and the clinical features of MPN patients rather than do CALR mutation. JAK2+ groups showed a tendency of poor PFS than JAK2- groups regardless of CALR mutation. CALR+ was a predictor of late response to the treatment. Our study also showed that thrombosis was more frequent in ET patients with type 2 CALR mutations than in those with type 1 CALR mutations.
Janus激酶2（JAK2）和钙网蛋白（CALR）是原发性血小板增多症（ET）中最常见的两种突变，据报道二者相互排斥。因此，我们检测了123例无BCR-ABL1重排的骨髓增殖性肿瘤（MPN）患者队列以及另外96例ET患者，以确定JAK2和CALR突变是否共存。123例MPN患者中CALR突变的发生率为20.3%；ET患者（n = 74）中为31.1%，原发性骨髓纤维化患者（n = 4）中为25%，真性红细胞增多症患者（n = 45）中为2.2%。167例ET患者中有7例（4.2%）JAK2和CALR突变共存。我们回顾了4组（JAK2+/CALR+、JAK2+/CALR-、JAK2-/CALR+、JAK2-/CALR-）患者的临床特征、无进展生存期（PFS）以及达到部分缓解的时间。与JAK2-/CALR-组相比，JAK2+/CALR-组白细胞计数和血红蛋白水平更高，血栓形成事件更频繁。JAK2突变对MPN患者的疾病表型和临床特征的影响大于CALR突变。无论CALR突变情况如何，JAK2+组的PFS均有比JAK2-组差的趋势。CALR+是治疗反应延迟的一个预测指标。我们的研究还表明，2型CALR突变的ET患者比1型CALR突变的患者血栓形成更频繁。
