Calreticulin gene mutation in hairy cell leukemia and relationship with prognosis

Objective: Hairy cell leukemia is a rare lymphoproliferative disorder. The pathogenesis of the disease is not completely understood. Calreticulin protein plays a role on homeostasis mechanism in the cell. It is synthesized as a result of pathological calreticulin gene mutation and JAK / STAT signaling pathway was found to cause activation. Calreticulin mutations were found to occur as a result of various homeostatic disorders and cancer. The aim of this study was to determine the presence of calreticulin gene mutation in hairy cell leukemia; additionally we aimed to assess clinical data of disease and relationship with their prognosis. Materials and Methods: In this single-center study, bone marrow biopsy tissue samples of 33 hairy cell leukemia patients whom were diagnosed between 2005-2015 were used. Some clinical and laboratory findings of the patients were studied as retrospectively. Following the isolation of genetic material and gene sequence analysis by PCR, mutations were investigated for calreticulin. Patient's age, gender, laboratory parameters and survival time were evaluated by statistical methods. Results: Of the 33 patient samples, 21 gene sequencing could be performed and calreticulin gene mutation was not detected in any. 26 patients (78.8%) were male and mean age was determined as 55.3 ± 13.3 years. Of the 33 patients, 23 received cladribine treatment with 13 (%56.5) patients achieved complete remission and 3 (%13) achieved partial remission. When assessed the presence of splenomegaly and monocytopenia; splenomegaly was significantly higher in patients without monocytopenia (p=0.05). There was survival differencies between treated (23 patients) and untreated (10 patients) patient group (p=0.001). The patients who treated had significantly longer overall survival compared to those untreated patients. Furthermore, median hemoglobin level was higher in remission group compared to non remission group as 10.1 g/dl vs 8.5 g/dL respectively and there was a statistically significant difference between them (p=0.047). Conclusion: This is the first study carried out regarding calreticulin gene mutation in Hairy Cell Leukemia in the literature. In our study, we obtained important information about the disease clinic, histopathology and prognostic features. As a result, spleen sizes were larger in patients with who had non-monocytopenia and hemoglobin levels were higher in remission group. This result may be an important finding in terms of timing of treatment in patients with Hairy Cell Leukemia.