Misawa Kyohei, Yasuda Hajime, Araki Marito, Ochiai Tomonori, Morishita Soji, Shirane Shuichi, Edahiro Yoko, Gotoh Akihiko, Ohsaka Akimichi, Komatsu Norio
Department of Hematology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Int J Hematol. 2018 Jun;107(6):673-680. doi: 10.1007/s12185-018-2421-7. Epub 2018 Feb 20.
The majority of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) harbor JAK2, CALR, or MPL mutations. We compared clinical manifestations of different subtypes of JAK2 and CALR mutations in Japanese patients with MPNs. Within our cohort, we diagnosed 166 patients as polycythemia vera (PV), 212 patients as essential thrombocythemia (ET), 23 patients as pre-primary myelofibrosis (PMF), 65 patients as overt PMF, and 27 patients as secondary myelofibrosis following the 2016 WHO criteria. Compared to patients with JAK2V617F-mutated PV, JAK2 exon 12-mutated PV patients were younger, showed lower white blood cell (WBC) counts, lower platelet counts, higher red blood cell counts, and higher frequency of thrombotic events. Compared to JAK2-mutated ET patients, CALR-mutated ET patients were younger, showed lower WBC counts, lower hemoglobin levels, higher platelet counts, and fewer thrombotic events. CALR type 1-like mutation was the dominant subtype in CALR-mutated overt PMF patients. Compared with JAK2V617F-mutated ET patients, JAK2V617F-mutated pre-PMF patients showed higher LDH levels, lower hemoglobin levels, higher JAK2V617F allele burden, and higher frequency of splenomegaly. In conclusion, Japanese patients with MPNs grouped by different mutation subtypes exhibit characteristics similar to those of their Western counterparts. In addition, ET and pre-PMF patients show different characteristics, even when restricted to JAK2V617F-mutated patients.
大多数费城染色体阴性骨髓增殖性肿瘤（MPN）患者携带JAK2、CALR或MPL突变。我们比较了日本MPN患者中不同亚型JAK2和CALR突变的临床表现。在我们的队列中，根据2016年世界卫生组织标准，我们诊断出166例患者为真性红细胞增多症（PV），212例患者为原发性血小板增多症（ET），23例患者为原发性骨髓纤维化前期（PMF），65例患者为明显的PMF，27例患者为继发性骨髓纤维化。与携带JAK2V617F突变的PV患者相比，携带JAK2外显子12突变的PV患者更年轻，白细胞（WBC）计数更低，血小板计数更低，红细胞计数更高，血栓形成事件的发生率更高。与携带JAK2突变的ET患者相比，携带CALR突变的ET患者更年轻，WBC计数更低，血红蛋白水平更低，血小板计数更高，血栓形成事件更少。CALR 1型样突变是携带CALR突变的明显PMF患者中的主要亚型。与携带JAK2V617F突变的ET患者相比，携带JAK2V617F突变的PMF前期患者乳酸脱氢酶（LDH）水平更高，血红蛋白水平更低，JAK2V617F等位基因负担更高，脾肿大的发生率更高。总之，按不同突变亚型分组的日本MPN患者表现出与其西方同行相似的特征。此外，即使仅限于携带JAK2V617F突变的患者，ET和PMF前期患者也表现出不同的特征。
