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Global Translational Medicine Genes and blood cells in Ph-negative MPNs

biomarker of thrombotic events in MPNs. Thrombosis is the importance of PLT, as the main source of PAI-1, in the
significantly and frequently observed in patients with the course of Ph-negative MPNs.
V617F mutation compared to those without. Patients with
JAK2V617F mutation-positive MPNs exhibit high levels 5. Conclusion
of hemoglobin and hematocrit, along with low levels of The JAK2V617F mutation was detected in 78.6% of patients
erythropoietin, an increase in WBC count, and a higher with newly diagnosed Ph-negative MPNs. In patients with
frequency of thrombosis. In addition, our study found ET, it is associated with a higher count of all blood cells.
7,28
that the V617F mutation in patients with ET is associated
with higher levels of WBCs, RBCs, and PLTs. The 4G/4G, 4G/5G, and 5G/5G genotypes of the PAI-1
gene were detected in patients with MPNs in 19.6%, 51.8%, and
It has been demonstrated that alterations in the 28.6% of cases, respectively, which is not significantly different
gene expression profile of megakaryocytes can lead to from their distribution in the general population and does not
circulating PLTs with altered hemostatic or inflammatory depend on the presence of a mutation in the JAK2 gene.
function. PLT activation can be caused by abnormalities
in hematopoietic stem cells due to dysfunction associated A relative increase in PLT count compared to RBC
with driver mutations that lead to hyperactive JAK2- count and WBC count was observed in patients with
dependent signaling. Furthermore, it was demonstrated MPNs. The heightened ratio of PLTs over RBCs is
45
that several genes involved in thrombin signaling and associated with −675 4G/5G polymorphism in the PAI-1
PLT activation were downregulated in CALR-mutated gene in patients with PV and PMF. In addition, in patients
patients in comparison to JAK2V617F-mutated ones. with PMF, the 4G/5G heterozygous genotype of the PAI-1
This observation correlates with a lower thrombotic gene is associated with a higher WBC count.
susceptibility in the former. 46 Acknowledgments
Furthermore, PLT activation can be initiated by None.
the overproduction of PLT and direct interaction with
activated leukocytes, endothelial cells, and various Funding
mediators. Consequently, the PLT transcriptome integrates
specific information obtained from both clonal cells and None.
megakaryocytes that are not involved in the malignant Conflict of interest
clone, as well as from the bone marrow microenvironment
and blood circulation, which largely determines their The authors declare that they have no competing interests.
activity. Consequently, transcriptome analysis and the
detection of changes in gene expression at a specific time Author contributions
point will facilitate a more profound comprehension of the Conceptualization: Yevhen Dzis
underlying mechanisms that contribute to PLT dysfunction Investigation: Yevhen Dzis, Myroslav Voroniak, Nataliia
in MPNs. 47 Shelep, Sofiia Khudzii, Ivan Dzis
The present study demonstrates that to assess the Methodology: Yevhen Dzis, Myroslav Voroniak
balance and kinetics of blood cells in patients with Writing – original draft: Yevhen Dzis, Oleksandra
Ph-negative MPNs and to choose optimal clinical Tomashevska
decisions, it is advisable to determine the ratio between Writing – review & editing: Yevhen Dzis, Oleksandra
different populations of blood cells along with the analysis Tomashevska
of quantitative parameters of the CBC. Using the ratio Ethics approval and consent to participate
between PLT and other blood cells in our study, we found
a relative increase in the PLT count compared to the RBC Ethical approval was sought and obtained in accordance
count in patients with Ph-negative MPNs, not only with with the World Medical Association (WMA) Declaration
ET but also with PV and PMF. Certain relationships were of Helsinki – Ethical Principles for Medical Research
identified between the count of peripheral blood cells and Involving Human Subjects, as well as the directives
mutations in the PAI-1 and JAK2 genes in these patients. outlined in the Ministry of Health of Ukraine No. 690
Further studies on a larger sample of patients using dated September 23, 2009, No. 944 dated December 14,
multivariate clinical and molecular genetic analysis are 2009, and No. 616 dated August 3, 2012.
needed to study the influence of the 4G/5G polymorphism Consent for publication
of the PAI-1 gene on the development of myelofibrosis and
prothrombotic disorders of hemostasis, as well as to study Not applicable.

Volume 3 Issue 2 (2024) 9 doi: 10.36922/gtm.2559