Type and frequency of chromosomal aberrations and importance of molecular JAK2V617F marker in primary myelofibrosis

Abstract

Primary Myelofibrosis (PMF) is a chronic, malignant hematological disease, characterized by leukoerythroblastic blood picture, anisopoikilocytosis teardrop-shaped erythrocyte, different degree of bone marrow fibrosis and hepatosplenomegaly due to extramedullary hematopoiesis. Among genetic specificities of the disease, those that stand out are chromosomal aberrations in pathological, myeloid blood cells and point mutation V617F in the JAK2 gene. The main goal of study was to examine karyotype and cytogenetic parameters and presence of JAK2V617F mutation in the genome of patients with de novo PMF. Additionally, other diagnostic parameters, their mutual correlations and their effect on cumulative survival rate of patients were examined. Karyotype analysis was performed by conventional cytogenetic method. Allelespecific PCR was used to detect the JAK2V617F mutation. The study used descriptive and analytical statistical methods. By retrospective analysis of cytogenetic results that included 61 patients, abnormal karyotype was registered in 41% of them. Specific PMF aberrations that were found are : 13q-, 20q-, +8, but also aberrations that are rarely present in this disease. Prospective study included 144 patients. The frequency of chromosomal aberrations was tested, so as the frequency of JAK2V617F mutation, their mutual correlation and correlation with clinical and hemato-laboratory parameters. Chromosomal aberrations were present in 29% of patients. Of specific aberrations for PMF, the most common was trisomy of chromosome 9, then 13q-and 20q-. JAK2V617F mutation was registered in 55% of patients. Examining the correlation between mutation and type of karyotype and mutation and chromosomal aberrations with various risk level, statistically significant difference was not registered (p=0.153). Examining the importance of clinical and hematological parameters, difference was registered in survival of patients with different prognostic groups applying Lille, Cervantes, IPSS, DIPSS prognostic systems (PSs) (for all p<0.001), Mayo PS for all patients (p=0.001) and Mayo PS for younger patients (p=0.013). Testing the influence of the JAK2V617F mutation, it was noticed that there is no statistically significant difference (p=0.807) in the survival of patients with and without mutations. Examining the importance of pathological karyotype and some chromosomal aberrations upon survival of patients, statistic significance (p=0.004) was registered using DIPSS cytogenetic prognostic system (CPS). Applying Lille, Mayo and IPSS CPSs, statistic significance was not registered (p=0.155 and p=0.214, p=0.152). Our results indicate that the overall frequency of chromosomal abnormalities in patients with PMF is 32%. The most common chromosomal aberrations are: +8, +9, 13q-and 20q-. The incidence of JAK2V617F somatic mutation is 55% in our PMF patients cohort. Correlation between chromosomal aberrations and JAK2V617F mutation was not found. It was also concluded that prognostically favorable chromosomal aberrations for patients with PMF ...