Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia.
Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia.
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DOI：
10.18632/oncotarget.10958
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发表时间：
2016-08-30
期刊：
影响因子：
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通讯作者：
Shin MG
中科院分区：
文献类型：
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作者：
Kang MG;Choi HW;Lee JH;Choi YJ;Choi HJ;Shin JH;Suh SP;Szardenings M;Kim HR;Shin MG
Janus激酶2（JAK 2）和钙网蛋白（CALR）构成了原发性血小板增多症（ET）中最常见的两种突变，据报道两者相互排斥。因此，我们研究了一个队列的123例骨髓增生性肿瘤（MPN）患者无BCR-ABL 1重排和额外的ET患者（n=96）的JAK 2和CALR突变的共存。在123例MPN患者中，CALR突变的频率为20.3%; ET（n=74）为31.1%，原发性骨髓纤维化（n=4）为25%，真性红细胞增多症（n=45）为2.2%。167例ET患者中有7例（4.2%）同时存在JAK 2和CALR突变。对4组（JAK 2 +/CALR+、JAK 2 +/CALR-、JAK 2-/CALR+、JAK 2-/CALR-）的临床特征、无进展生存期（PFS）和达到部分缓解的时间进行了审查。JAK 2 +/CALR-组的白细胞计数和血红蛋白水平高于JAK 2-/CALR-组，血栓形成事件发生率高于JAK 2-/CALR-组。JAK 2突变对MPN患者的疾病表型和临床特征的影响大于CALR突变。JAK 2+组显示出比JAK 2-组差的PFS趋势，无论CALR突变如何。CALR+是治疗晚期反应的预测因子。我们的研究还表明，血栓形成更频繁的ET患者与2型CALR突变比1型CALR突变。
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.