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

Abstract

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.

Efficacy and safety of anagrelide as a first‐line drug in cytoreductive treatment‐naïve essential thrombocythemia patients in a real‐world setting

“…The findings of increased WBC count, neutrophil rate, and Hb level in the JAK2 ‐ET group in our cohort, compared with the CALR ‐ET group, are consistent with previously reported findings . In addition, the lack of a significant difference in platelet count between the two groups might be due to the small sample size of our cohort.…”

“…The findings of increased WBC count, neutrophil rate, and Hb level in the JAK2-ET group in our cohort, compared with the CALR-ET group, are consistent with previously reported findings. 30,31 In addition, the lack of a significant difference in platelet count between the two groups might be due to the small sample size of our cohort. There was no significant difference in the median daily dose F I G U R E 2 Median platelet count before and after treatment in each of the three groups.…”

Clinical and Hematological Relevance of JAK2V617F, CALR, and MPL Mutations in Vietnamese Patients with Essential Thrombocythemia

“…Using ASO-PCR and conventional Sanger sequencing method, we found that 84.8% of 395 ET patients carried JAK2V617F, CALR, or MPL mutations, underscoring the importance of combined genetic tests for diagnosis of ET patients. The JAK2V617F was the most frequent mutation (56.2%), followed by CALR mutation (27.6%), which is consistent with Chinese (Lin et al, 2015), Japanese (Misawa et al, 2018), Argentinean (Ojeda et al, 2018), and American (Tefferi et al, 2014) ET populations. However, the frequency of CALR exon 9 mutations in our study is higher than that of Thai (Limsuwanachot et al, 2017), Korean (Kim et al, 2015) , Italian (Rotunno et al, 2014) , Polish (Wojtaszewska et al, 2015) , and Brazilian (Nunes et al, 2015) ET patients; in those populations the mutation rate of CALR exon 9 mutations ranged from 12.5% to 15.5%.…”

Gene expressions involved in immune system control and serum CA125 content in polycythemia vera. Tap

“…Nồng độ LDH tăng cao dẫn đến tăng nồng độ lactat trong máu và tổn thương mô. Chỉ số LDH tăng liên quan đến mức độ nặng của bệnh đã được chỉ ra trong một nghiên cứu gần đây trên bệnh nhân THCVC (Misawa et al, 2018). Ngoài ra, các chỉ số hóa sinh khác như ure, glucose, ferritin, AST và ALT cũng có một số bệnh nhân có các chỉ số này cao hơn bình thường.…”