The PAI-1 4G/5G polymorphism, JAK2V617F mutation, and their associations with blood cells in Ph-negative myeloproliferative neoplasms

Factors influencing the urokinase-type plasminogen activator system play important roles in pathogenetic processes in Ph-negative myeloproliferative neoplasms (MPNs). In addition, the JAK2V617F mutation is a key determinant of outcomes in these diseases. This study evaluated complete blood count (CBC) parameters, the plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphism, and the JAK2V617F mutation in patients with Ph-negative MPNs, aiming to identify possible associations between them. We analyzed results from 56 patients newly diagnosed with Ph-negative MPNs— essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF)—before treatment initiation. The CBC of 475 people from a diagnostic center database served as a population sample for comparison. In patients with Ph-negative MPNs, PAI-1 genotypes 4G/4G, 4G/5G, and 5G/5G were detected in 11 (19.6%), 29 (51.8%), and 16 (28.6%) cases, respectively. No significant differences in genotype distribution were found among ET, PV, and PMF patients. PMF patients with the 4G/5G genotype had a higher white blood cell (WBC) count compared to those with the 5G/5G genotype (P = 0.027). The JAK2V617F mutation was found in 44 (78.6%) patients. ET patients with this mutation (n = 13) exhibited significantly higher counts of platelets (PLTs), red blood cells (RBCs), and WBCs compared to those without it. The PLT/RBC ratio was significantly higher in all disease categories compared to the population sample, with the highest ratios in ET patients. The PLT/WBC ratio in ET and PV patients was also higher than in the population sample (P < 0.05). This relative thrombocytosis is likely clonal in origin, associated with genes responsible for PLT quantitative parameters, JAK-STAT signaling pathway proteins, and factors in the uPA-uPAR-PAI-1/PAI-2 system. These genes share common loci in chromosomes (1p34.1-p34.3, 7q21.1-q21.3, 9p24.1, 19p13.11-p13.2, and 19q13.31-q13.32). Due to their close spatial proximity, these genes can form genetic complexes and mutually influence their expression levels, thereby contributing to the unique pathogenesis of these diseases.