PB2198 CRUCIAL AGE FOR JAK2 V617F MUTATION: GENDER DIFFERENCES

Abstract

Background:The prevalence of JAK2 V617F mutation of Ph‐negative myeloproliferative neoplasias (MPN) increases with age. The dependence of the JAK2 V617F mutation prevalence and the rate of increasing its burden from the patients sex was discussion [Patterson‐Fortin J, et al., 2017; Stein BL et al., 2010]. There is monotonically increasing curve of somatic mutations and oncological morbidity as a usual presentation of growth graphs. However, the using of the population threshold model of the age dynamics of oncological diseases makes it possible to set of critical points of inflection (second order phase transition) and to quantify the intensity of the increase in the burden of disease [Landau LD, Lifshitz EM, 2013; Soukhovolsky VG et al., 2015].Aims:Assessment of the intensity of the JAK2 V617F mutation prevalence on the age and sex dependence using the model of the “second order phase transition”.MethodsThe data base of the Krasnoyarsk branch of the National Hematology Research Center from Jan 2012 to Feb 2019 examination has been used. The JAK2V617F allele burden was measured in whole blood samples by an allele‐specific quantitative polymerase chain reaction using of the “Myeloskrin JAK2 kit” (Formula of gene ltd). The relationship between the q (rate of JAK2 V617F detection) and the 1/T indicator (“reverse age”) in each age‐old five‐year cohort on 1154 men and 958 women referred with suspicion of MPN was studied. The values of q2 should be close to zero as according to the model of second order phase transitions for physical systems until reaching a certain critical patients age Tc and the relationship between the q2 and 1/T variables will be described by the equation q2 = a‐b/T with an angular coefficient b characterizing the increase in the intensity of the mutational burden with age after reaching the critical age Tc.Results:Using of our model led to transforms the monotonous growth curve of mutation prevalence with age. The value of q2 is close to zero at high values of 1/T (young patients) and for smaller values of 1/T (more older age) the relationship between q2 and 1/T becomes linear (figure). The hypothesis of the statistical significance differences of regression for male and female was tested by Fisher test for the significance level α=5%. Hypothesis of the absence of differences between the two regressions is not rejected. The critical age of patients transition to the phase with a high risk of mutation development corresponds for male Tc = 48.8 years and for female Tc = 36.0 years. Intensity of further accumulation of the mutation burden in male b = 44.35 ± 12.86, in female b = 27.52 ± 4.57.Summary/Conclusion:The “second order phase transitions model” it possible to introduce in the population analysis the indicators of the “critical age” Tc and the intensity of accumulation of the burden of mutations b. This estimate are not significantly different for male and female for our sample. The calculated critical age turned out to be significantly lower than the median of the age of diagnosis of MPN (53 and 57 years). The proposed model will be useful for analyzing the characteristics of the population of MPN in different cohorts, as well as in different social and environmental conditions of life.image