International Journal of Hematology

, Volume 107, Issue 6, pp 673–680 | Cite as

Mutational subtypes of JAK2 and CALR correlate with different clinical features in Japanese patients with myeloproliferative neoplasms

  • Kyohei Misawa
  • Hajime Yasuda
  • Marito Araki
  • Tomonori Ochiai
  • Soji Morishita
  • Shuichi Shirane
  • Yoko Edahiro
  • Akihiko Gotoh
  • Akimichi Ohsaka
  • Norio Komatsu
Original Article


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.


CALR Driver mutations JAK2 exon 12 JAK2V617F MPL 



We thank Masaaki Noguchi (Juntendo Urayasu Hospital), Michiaki Koike (Juntendo shizuoka Hospital) and Takao Hirano (Juntendo Nerima Hospital) for providing patient specimens and clinical data; Satoshi Tsuneda and Yuji Sekiguchi for their generous support and encouragement; Kyoko Kubo, Kazuko Kawamura, and Megumi Hasegawa for their superb secretarial assistance.

Compliance with ethical standards

Conflict of interest

This study was carried out as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), The Japan Agency for Medical Research and Development, and Ministry of Education, Culture, Sports, Science and Technology of Japan. Part of this work was supported by Japan Society for the Promotion of Science KAKENHI Grant #17H04211. The authors have no conflict of interest to declare.

Supplementary material

12185_2018_2421_MOESM1_ESM.docx (15 kb)
Table S1. Clinical characteristics of JAK2V617F-mutated and triple-negative pre-PMF patients. ET: essential thrombocythemia; pre-PMF: prefibrotic primary myelofibrosis. WBC: white blood cell; Hb: hemoglobin Hct: hematocrit; LDH: lactate dehydrogenase. For continuous variables, data are shown as median values and brackets represent range. For categorical variables, right side of / represents the total number of patients studied and left side represents the number of positive patients, and brackets represent positive percentages. *There was only one CALR-mutated pre-PMF patient, and thus was removed from analysis here (DOCX 15 kb)
12185_2018_2421_MOESM2_ESM.docx (15 kb)
Table S2. Clinical characteristics of JAK2V617F-mutated ET and JAK2V617F-mutated pre-PMF patients. JAK2-ET: JAK2V617F-mutated essential thrombocythemia; JAK2-pre-PMF: JAK2V617F-mutated prefibrotic primary myelofibrosis. WBC: white blood cell; Hb: hemoglobin; Hct: hematocrit; LDH: lactate dehydrogenase. For continuous variables, data are shown as median values and brackets represent range. For categorical variables, right side of / represents the total number of patients studied and left side represents the number of positive patients, and brackets represent positive percentage (DOCX 15 kb)


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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.Department of HematologyJuntendo University Graduate School of MedicineTokyoJapan
  2. 2.Department of Transfusion Medicine and Stem Cell RegulationJuntendo University Graduate School of MedicineTokyoJapan

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