Contributions
Abstract: EP1112
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
Myeloproliferative neoplasms (MPN) are a group of clonal hematological malignancies. In which there are three classic pathologies (WHO 2017): polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF). According to the accumulated data, it becomes clear that the traditional division of MPN into the above mentioned subtypes does not fully reflect the main biological heterogeneity of these diseases, and that their clinical and laboratory parameters are the result of the various genetic factors interaction. Somatic point mutations of genes encoding tyrosine kinase (JAK2), calreticulin protein (CALR), and thrombopoietin receptor (MPL) (driver mutations, DM) had a great influence on the diagnosis of this group of pathological conditions. However, the question of the each of the mutations influence on the fenotype remains open.
Aims
To determine the correlation of the gene mutations JAK2, CALR, MPL with the clinical and laboratory features of MPN.
Methods
Retro- and prospective study of the 192 ET and 141 PMF patient’s medical histories were performed. All of them were observed at The Federal State-Financed Scientific Institution Kirov Research Institute of Hematology and Blood Transfusion under the Federal Medical Biological Agence from 1995 to 2019. Gene mutations JAK2 V617F, CALR, and MPL W515L/K were determined using kits from GenoTechnologiya LLC (Moscow, Russia) by real-time PCR using TaqMan technology. The mutational status of the gene CALR included two like mutations - p.L367fs * 46 (52 bp deletion - type 1, or group CALR1+) and p.K385fs * 47 (5 bp insertion - type 2, or group CALR2+). Patients without DM were assigned to the triple negative group. The statistical significance of quantitative indicators differences was assessed by the Kruskal-Wallace test.
Results
JAK2-mutated (JAK2+) ET patients display a higher hemoglobin levels (median Hb levels are 147 (102-219) and 134 (93-176) g/l, respectively, p <0.0001). Patients with CALR2+ had a higher number of platelets compared with those who did not have this mutation (median platelet counts 1197x109/l (676-3766) and 750x109/l (357-2074), respectively, p <0.0001). A comparative analysis of the data obtained showed that the CALR2+ ET patients were significantly younger at the onset of the disease than the patients from other groups (medians of age 39 (31-78) and 57 (18-90) years, respectively, p = 0.001)
Patients with JAK2 V617F mutated PMF also had higher hemoglobin levels (median Hb levels are 146 (125-162) and 114 (59-160) g/l, respectively, p <0.0001). The number of platelets in CALR2+ mutation carriers was statistically significantly higher than their number in patients from other groups (median platelet counts are 1330x109/l (272-2529) and 487x109/l (38-2000), respectively, p = 0.01). The presence of a type 1 CALR gene mutation in patients was associated with a lower leukocyte count of the median leukocyte count of 6.3x109/l (3.35-13.64) and 12.2x109/l (2.3-49.1), respectively, p = 0.0004).
Conclusion
In patients with ET and PMF, the association of the gene JAK2 V617F mutation with a higher hemoglobin level was confirmed. Patients with type 2/like gene CALR mutations in comparison with all other patients had the highest platelet count. In the case of PMF, it was found that the leukocyte count in patients with a type 1 gene CALR mutation was lower than in patients from other groups. A statistically significant difference in the age at the disease onset for ET was established.
Keyword(s): Essential Thrombocytemia
Abstract: EP1112
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
Myeloproliferative neoplasms (MPN) are a group of clonal hematological malignancies. In which there are three classic pathologies (WHO 2017): polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF). According to the accumulated data, it becomes clear that the traditional division of MPN into the above mentioned subtypes does not fully reflect the main biological heterogeneity of these diseases, and that their clinical and laboratory parameters are the result of the various genetic factors interaction. Somatic point mutations of genes encoding tyrosine kinase (JAK2), calreticulin protein (CALR), and thrombopoietin receptor (MPL) (driver mutations, DM) had a great influence on the diagnosis of this group of pathological conditions. However, the question of the each of the mutations influence on the fenotype remains open.
Aims
To determine the correlation of the gene mutations JAK2, CALR, MPL with the clinical and laboratory features of MPN.
Methods
Retro- and prospective study of the 192 ET and 141 PMF patient’s medical histories were performed. All of them were observed at The Federal State-Financed Scientific Institution Kirov Research Institute of Hematology and Blood Transfusion under the Federal Medical Biological Agence from 1995 to 2019. Gene mutations JAK2 V617F, CALR, and MPL W515L/K were determined using kits from GenoTechnologiya LLC (Moscow, Russia) by real-time PCR using TaqMan technology. The mutational status of the gene CALR included two like mutations - p.L367fs * 46 (52 bp deletion - type 1, or group CALR1+) and p.K385fs * 47 (5 bp insertion - type 2, or group CALR2+). Patients without DM were assigned to the triple negative group. The statistical significance of quantitative indicators differences was assessed by the Kruskal-Wallace test.
Results
JAK2-mutated (JAK2+) ET patients display a higher hemoglobin levels (median Hb levels are 147 (102-219) and 134 (93-176) g/l, respectively, p <0.0001). Patients with CALR2+ had a higher number of platelets compared with those who did not have this mutation (median platelet counts 1197x109/l (676-3766) and 750x109/l (357-2074), respectively, p <0.0001). A comparative analysis of the data obtained showed that the CALR2+ ET patients were significantly younger at the onset of the disease than the patients from other groups (medians of age 39 (31-78) and 57 (18-90) years, respectively, p = 0.001)
Patients with JAK2 V617F mutated PMF also had higher hemoglobin levels (median Hb levels are 146 (125-162) and 114 (59-160) g/l, respectively, p <0.0001). The number of platelets in CALR2+ mutation carriers was statistically significantly higher than their number in patients from other groups (median platelet counts are 1330x109/l (272-2529) and 487x109/l (38-2000), respectively, p = 0.01). The presence of a type 1 CALR gene mutation in patients was associated with a lower leukocyte count of the median leukocyte count of 6.3x109/l (3.35-13.64) and 12.2x109/l (2.3-49.1), respectively, p = 0.0004).
Conclusion
In patients with ET and PMF, the association of the gene JAK2 V617F mutation with a higher hemoglobin level was confirmed. Patients with type 2/like gene CALR mutations in comparison with all other patients had the highest platelet count. In the case of PMF, it was found that the leukocyte count in patients with a type 1 gene CALR mutation was lower than in patients from other groups. A statistically significant difference in the age at the disease onset for ET was established.
Keyword(s): Essential Thrombocytemia