PB2234 MUTATIONAL SIGNATURES AFFECT THE PHENOTYPIC PRESENTATION OF DISEASE SUBTYPES IN MPN PATIENTS FROM BOSNIA AND HERZEGOVINA

Background: Philadelphia‐negative myeloproliferative neoplasms (MPNs), including PV, ET, PMF, and MPN‐U are a group of clonal myeloid disorders characterized by myeloproliferation without dysplasia. WHO 2016 revision lists the presence of driver mutations as one of several major criteria in the diagnosis of MPN patients. MPN subtypes have overlapping clinical symptoms and a common molecular basis.Aims:The aim of this study was to evaluate disease phenotypes and evolution in regards to the detected JAK2, CALR and MPL mutations in the population of MPN patients in Bosnia and Herzegovina. Also, we compared hematologic and clinical features of ET patients carrying either JAK2 or CALR mutations with JAK2 positive PV patients in order to determine the correlation of clinical features and disease evolution.Methods:A cohort of 138 patients diagnosed with MPN and treated at Clinical Center of the University of Sarajevo and Cantonal Hospital Zenica, in the period from January 2000 to June 2018 were included in this retrospective study. Analyzed patients were subcategorized according to BCR‐ABL negative MPN subtypes: ET (n = 41), PV (n = 56), PMF (n = 10), and MPN‐U (n = 31). Patients characteristics included full blood count, bone marrow characteristics, hepato/splenomegaly, overall survival as well as mutational status of JAK2, CALR, and MPL genes. Comparisons of quantitative variables between groups of patients were carried out by one‐way ANOVA. Correlation between numerical variables was tested by the Spearman's coefficient. Survival probabilities were estimated with the Kaplan‐Meier method and compared using the log‐rank test. Data were analyzed using IBM SPSS v.21.Results:In the present work, we compared hematologic and clinical features of patients with JAK2‐mutated ET with those of patients with CALR‐mutated ET and related the findings to features observed in patients with PV. Median follow‐up was 33 months (50, 45.5, 69 and 20 months for PV, ET, PMF and MPN‐U subtypes, respectively). We found that JAK2 V617F+ patients had higher values for RBC, Hb and Hct compared to CALR+ patients (p<0.05). MPL+ patients had higher values for Plt compared to JAK2 V617F+ patients (p<0.05). The mutant allele burden in JAK2 V617F+ PV and ET patients was directly correlated with hematological parameters (ρ = 0.36, ρ = 0.14, and ρ = 0.21 for Hb, RBC, and Hct, respectively) and inversely correlated with Plt count (ρ = −0.12). JAK2 V617F+ patients had worse survival compared to CALR+ and MPL+ patients, eventhough significant differences were not found (p > 0.05).Summary/Conclusion:Mutant allele burden is a determinant of the clinical phenotypic features in JAK2 V617F MPN patients. Mutational profile define clinical course and outcomes in MPN subtypes.