Page 65 - GTM-3-2

Global Translational Medicine

ORIGINAL RESEARCH ARTICLE
The PAI-1 4G/5G polymorphism, JAK2V617F

mutation, and their associations with blood cells
in Ph-negative myeloproliferative neoplasms

Yevhen Dzis * , Oleksandra Tomashevska , Myroslav Voroniak²,
1
1
Nataliia Shelep², Sofiia Khudzii², and Ivan Dzis 3
1 Department of Internal Medicine No. 2, Faculty of Dentistry, Danylo Halytsky Lviv National Medical
University, Lviv, Lviv Oblast, Ukraine
²Laboratory of Molecular Genetics, Institute of Blood Pathology and Transfusion Medicine of the
National Academy of Medical Sciences of Ukraine, Lviv, Lviv Oblast, Ukraine
3 Department of Therapy, Medical Diagnostics, Hematology and Transfusiology, Faculty of
Postgraduate Education, Danylo Halytsky Lviv National Medical University, Lviv, Lviv Oblast, Ukraine

Abstract
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—
*Corresponding author: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis
Yevhen Dzis (PMF)—before treatment initiation. The CBC of 475 people from a diagnostic center
(dzis_yevhen@meduniv.lviv.ua)
database served as a population sample for comparison. In patients with Ph-negative
Citation: Dzis Y, Tomashevska O, MPNs, PAI-1 genotypes 4G/4G, 4G/5G, and 5G/5G were detected in 11 (19.6%),
Voroniak M, Shelep N, Khudzii S,
Dzis I. The PAI-1 4G/5G 29 (51.8%), and 16 (28.6%) cases, respectively. No significant differences in genotype
polymorphism, JAK2V617F distribution were found among ET, PV, and PMF patients. PMF patients with the 4G/5G
mutation, and their associations genotype had a higher white blood cell (WBC) count compared to those with the
with blood cells in Ph-negative
myeloproliferative neoplasms. 5G/5G genotype (P = 0.027). The JAK2V617F mutation was found in 44 (78.6%) patients.
Global Transl Med. 2024;3(2):2559. ET patients with this mutation (n = 13) exhibited significantly higher counts of platelets
doi: 10.36922/gtm.2559 (PLTs), red blood cells (RBCs), and WBCs compared to those without it. The PLT/RBC ratio
Received: December 28, 2023 was significantly higher in all disease categories compared to the population sample,
Accepted: April 18, 2024 with the highest ratios in ET patients. The PLT/WBC ratio in ET and PV patients was also
Published Online: June 19, 2024
higher than in the population sample (P < 0.05). This relative thrombocytosis is likely
Copyright: © 2024 Author(s). clonal in origin, associated with genes responsible for PLT quantitative parameters,
This is an Open-Access article JAK-STAT signaling pathway proteins, and factors in the uPA-uPAR-PAI-1/PAI-2 system.
distributed under the terms of the
Creative Commons Attribution These genes share common loci in chromosomes (1p34.1-p34.3, 7q21.1-q21.3, 9p24.1,
License, permitting distribution, 19p13.11-p13.2, and 19q13.31-q13.32). Due to their close spatial proximity, these
and reproduction in any medium, genes can form genetic complexes and mutually influence their expression levels,
provided the original work is
properly cited. thereby contributing to the unique pathogenesis of these diseases.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Ph-negative myeloproliferative neoplasms; PAI-1 4G/5G polymorphism;
regard to jurisdictional claims in
published maps and institutional JAK2V617F mutation; Complete blood count
affiliations.

Volume 3 Issue 2 (2024) 1 doi: 10.36922/gtm.2559