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Updated: Sep 18, 2025
Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm
Published on: December 22, 2016
CalR and MPL Driver Mutations and Their Role in the Diagnosis and Clinical Course of JAK2-Unmutated Chronic
Tarık Onur Tiryaki1, Aynur Dağlar Aday2, Meliha Nalçacı1
1Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Istanbul University, Istanbul 34134, Turkey.
Abstract:
Background and Objectives: Philadelphia (Ph)-negative myeloproliferative neoplasms can exhibit defects in Janus kinase 2 (JAK2), Calreticulin (CalR), and MPL genes. It is possible that the presence of other driver mutations may influence diagnosis and prognosis in patients who do not have a JAK2 gene mutation. The purpose of this study was to assess the frequency of CalR and MPL gene mutations and the clinical effects of these mutations in JAK2 gene-unmutated MPN patients from a single center. Materials and Methods: We examined 46 patients (ET/PMF: 34/12) diagnosed with MPNs regarding their genetic conditions, diagnoses, and complications. Results: CalR Type 1 gene mutation was detected in 26.1% of cases, CalR Type 2 gene mutation in 13.0%, MPL-L gene mutation in 2.2%, and MPL-K gene mutation in 6.5%. In total, 56.5% of patients were triple-negative. The presence of CalR Type 1 and Type 2 mutations was significantly more prevalent in patients with essential thrombocytosis (ET), although the difference did not reach statistical significance (p = 0.51, p = 0.57). In contrast, MPL mutations were only observed in patients with primary myelofibrosis (PMF). Conclusions: We found no correlation between thrombosis, leukemic transformation, and driver mutations. MPL gene mutation was present in only myelofibrosis patients, and CALR gene mutation was present in one of the three cases of leukemic transformation. The triple-negative group had a lower survival rate, but this difference was not statistically significant (110.3 months vs. 121.4 months, respectively, p = 0.53). However, the sample size was quite small. Our limited observations suggest a possible trend that requires confirmation.
Insights
This study investigated Calreticulin (CalR) and MPL gene mutations in Philadelphia-negative myeloproliferative neoplasms without JAK2 mutations. While CALR mutations were more common in essential thrombocytosis and MPL in primary myelofibrosis, no significant clinical correlations were found in this small cohort.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Philadelphia-negative myeloproliferative neoplasms (MPNs) can involve mutations in Janus kinase 2 (JAK2), Calreticulin (CALR), and MPL genes.
- Investigating co-occurring mutations in JAK2-unmutated MPNs is crucial for understanding diagnosis and prognosis.
Purpose of the Study:
- To determine the frequency of CALR and MPL gene mutations in JAK2-unmutated MPN patients.
- To evaluate the clinical impact of these mutations on diagnosis and complications within a single center.
Main Methods:
- Genetic analysis of 46 patients diagnosed with MPNs (Essential Thrombocytosis/Primary Myelofibrosis).
- Assessment of CALR (Type 1, Type 2) and MPL (MPL-L, MPL-K) gene mutations.
- Correlation of mutation status with clinical diagnoses and complications.
Main Results:
- CALR Type 1 mutations found in 26.1%, CALR Type 2 in 13.0%, MPL-L in 2.2%, and MPL-K in 6.5% of patients.
- 56.5% of patients were triple-negative for these mutations.
- MPL mutations were exclusively observed in primary myelofibrosis patients; CALR mutations showed a non-significant trend in essential thrombocytosis.
Conclusions:
- No significant correlation was identified between driver mutations and thrombosis or leukemic transformation.
- MPL mutations were specific to primary myelofibrosis, while CALR mutations appeared in one case of leukemic transformation.
- The triple-negative group exhibited a trend towards lower survival, though not statistically significant, highlighting the need for larger studies.
