Contributions
Abstract: PB2306
Type: Publication Only
Background
JAK2 exon 12 somatic mutations are highly specific to confirm the diagnosis of polycythemia vera (PV) (Pardanani A et al, Leukemia, 2007). It is known patients with JAK2 exon 12 mutated PV have isolated erythrocytosis and a younger age than patients with JAK2 V617F mutated PV (Scott L et al, N Engl J Med, 2007; Passamonti F et al, Blood, 2011).
Aims
This study aims to assess the clinical and molecular characteristics of patients with JAK2 exon 12 mutated PV from Krasnoyarsk region, Russia.
Methods
6 patients with JAK2 exon 12 mutated PV were involved in this study. The informed consents of these patients were obtained. The PV diagnosis of №1, 2, 3, 5 and 6th patient was confirmed by bone marrow trephine biopsies histological examination. JAK2 exon 12 mutation analysis was performed by heteroduplex analysis with separation of the PCR product by electrophoresis on non-denaturing PAGE (Subbotina T et al, Haematologica 2017). The identification of the JAK2 exon 12 mutation types and allele burden measurement was carried out by pyrosequencing (Subbotina T et al, Haematologica 2014). Clinical and laboratory data were collected from the time of initial diagnosis to the present. JAK2 exon 12 varianceMUT was calculated as a measure of relative changes in allele burden between the baseline and follow-up sample (Theocharides A et al, Haematologica, 2008).
Results
Some clinical and laboratory characteristics of 6 patients with JAK2 exon 12 mutated PV are reported in Table 1. The subjects were both men and women. Age of disease onset in subjects was from 28 to 72 year. Three out of these patients became ill before the age of 30 years. Duration of the disease is different: from 3 to 12 years. All 6 patients have an increased number of red blood cells, along with an accompanying increase in the concentration of hemoglobin and hematocrit level in the peripheral blood. Some of them had moderate increase number of leukocytes and platelets in the disease dynamics. All 6 patients have different mutation variant in the 12 exon of the JAK2: N542-E543del (c.1624_1629delAATGAA); I540-E543delinsKK (с.1619_1627 TCAgAAATg>AAA); N542_E543del (c.1623_1628delAAATGA); R541_E543>K (c.1622_1627delGAAATG); F537_K539>L (c.1611_1616delTCACAA); H538_K539>L (c.1612_1616CACAA>TT), accordingly. These mutations have been already described and included in the COSMIC website. Two out of six patients also have a mutation JAK2V617. JAK2 exon 12 allele burdens in the sample from №1 patient are significantly increased in the disease dynamics. № 1,2,5 patients in the anamnesis had splenomegaly. № 2,4,5 patients in the anamnesis had any thrombotic events. № 2-4 patients were treated phlebotomy only and did not receive any cytoreductive treatment to date. №5 and №6 patients receive hydroxyurea (HU). №1 patient was treated only with phlebotomy until 2016. Since 2017 cytoreductive therapy with HU has been started, but this causes to the development of hydroxyurea-induced thrombocytopenia to I-II degree. Carrying out of bone marrow trephine biopsies histological examination in 2015 years was confirmed PV and in 2017 – fibrosis manifestations. Thus, in №1 patient simultaneously with the allele burden increase develops disease progression – the initial manifestations of the transition of the PV to myelofibrosis. Thrombotic events have not been identified.
Conclusion
We confirm an earlier age of disease onset, as well as the presence of isolated erythrocytosis in patients with JAK2 exon 12 mutated PV. The increase of the allele burden level detected in one patient is accompanied with disease progression.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): mutation analysis, Myeloproliferative disorder, Polycythemia vera, Somatic mutation
Abstract: PB2306
Type: Publication Only
Background
JAK2 exon 12 somatic mutations are highly specific to confirm the diagnosis of polycythemia vera (PV) (Pardanani A et al, Leukemia, 2007). It is known patients with JAK2 exon 12 mutated PV have isolated erythrocytosis and a younger age than patients with JAK2 V617F mutated PV (Scott L et al, N Engl J Med, 2007; Passamonti F et al, Blood, 2011).
Aims
This study aims to assess the clinical and molecular characteristics of patients with JAK2 exon 12 mutated PV from Krasnoyarsk region, Russia.
Methods
6 patients with JAK2 exon 12 mutated PV were involved in this study. The informed consents of these patients were obtained. The PV diagnosis of №1, 2, 3, 5 and 6th patient was confirmed by bone marrow trephine biopsies histological examination. JAK2 exon 12 mutation analysis was performed by heteroduplex analysis with separation of the PCR product by electrophoresis on non-denaturing PAGE (Subbotina T et al, Haematologica 2017). The identification of the JAK2 exon 12 mutation types and allele burden measurement was carried out by pyrosequencing (Subbotina T et al, Haematologica 2014). Clinical and laboratory data were collected from the time of initial diagnosis to the present. JAK2 exon 12 varianceMUT was calculated as a measure of relative changes in allele burden between the baseline and follow-up sample (Theocharides A et al, Haematologica, 2008).
Results
Some clinical and laboratory characteristics of 6 patients with JAK2 exon 12 mutated PV are reported in Table 1. The subjects were both men and women. Age of disease onset in subjects was from 28 to 72 year. Three out of these patients became ill before the age of 30 years. Duration of the disease is different: from 3 to 12 years. All 6 patients have an increased number of red blood cells, along with an accompanying increase in the concentration of hemoglobin and hematocrit level in the peripheral blood. Some of them had moderate increase number of leukocytes and platelets in the disease dynamics. All 6 patients have different mutation variant in the 12 exon of the JAK2: N542-E543del (c.1624_1629delAATGAA); I540-E543delinsKK (с.1619_1627 TCAgAAATg>AAA); N542_E543del (c.1623_1628delAAATGA); R541_E543>K (c.1622_1627delGAAATG); F537_K539>L (c.1611_1616delTCACAA); H538_K539>L (c.1612_1616CACAA>TT), accordingly. These mutations have been already described and included in the COSMIC website. Two out of six patients also have a mutation JAK2V617. JAK2 exon 12 allele burdens in the sample from №1 patient are significantly increased in the disease dynamics. № 1,2,5 patients in the anamnesis had splenomegaly. № 2,4,5 patients in the anamnesis had any thrombotic events. № 2-4 patients were treated phlebotomy only and did not receive any cytoreductive treatment to date. №5 and №6 patients receive hydroxyurea (HU). №1 patient was treated only with phlebotomy until 2016. Since 2017 cytoreductive therapy with HU has been started, but this causes to the development of hydroxyurea-induced thrombocytopenia to I-II degree. Carrying out of bone marrow trephine biopsies histological examination in 2015 years was confirmed PV and in 2017 – fibrosis manifestations. Thus, in №1 patient simultaneously with the allele burden increase develops disease progression – the initial manifestations of the transition of the PV to myelofibrosis. Thrombotic events have not been identified.
Conclusion
We confirm an earlier age of disease onset, as well as the presence of isolated erythrocytosis in patients with JAK2 exon 12 mutated PV. The increase of the allele burden level detected in one patient is accompanied with disease progression.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): mutation analysis, Myeloproliferative disorder, Polycythemia vera, Somatic mutation