Page 70 - GTM-3-2

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

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Figure 1. The (A) C×PLT/RBC index and (B) PLT/WBC ratios in patients with essential thrombocythemia (Group 1), polycythemia vera (Group 2), and
primary myelofibrosis (Group 3). Group 4 represents the control
Abbreviations: PLT: Platelet; RBC: Red blood cell; WBC: White blood cell.

The frequency of the 4G allele was 40.9% in ET patients, PMF, those with the 4G/5G genotype had significantly
47.4% in PV patients, and 50.0% in PMF patients. There higher WBC counts compared to patients with the
were no significant differences in the detection rates of 5G/5G genotype, specifically 9.60 (8.49 – 11.19) × 10 /L
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4G/4G, 4G/5G, and 5G/5G genotypes or the 4G allele vs. 7.31 (5.10 – 8.30) × 10 /L (P = 0.027). In addition, in
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among the groups of patients with ET, PV, and PMF. patients with the 4G/4G genotype, there was a tendency
In addition, no significant differences were found in toward higher WBC counts compared to patients with
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the distribution of alleles and genotypes of the 4G/5G the 5G/5G genotype, 10.04 (9.70 – 11.70) × 10 /L vs.
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polymorphic locus of the PAI-1 gene in patients with ET, 7.31 (5.10 – 8.30) × 10 /L (P = 0.081). In patients with ET,
PV, and PMF compared to the general population sample. 24 those with the 4G/4G genotype demonstrated a tendency
Three patients with Ph-negative MPNs and thrombotic toward a lower C×PLT/RBC index compared to patients
complications at the time of diagnosis had PAI-1 gene with the 5G/5G genotype, specifically 2.53 (2.46 – 3.78) vs.
4G/4G or 4G/5G polymorphisms, along with mutations 3.81 (3.70 – 4.27) (P = 0.083) (Table 2).
in the prothrombin (G20210A), FV Leiden (G1691A), In patients with ET, both ICIs were significantly higher
or folate cycle enzyme genes, and were associated with across subgroups with different genotypes compared to
hyperhomocysteinemia. the control group. This finding reflects a predominance of
thrombocytopoiesis over erythropoiesis and leukopoiesis,
The molecular genetic analysis of the polymorphic locus
−675 4G/5G of the PAI-1 gene in 44 patients with MPNs regardless of −675 4G/5G polymorphism in the PAI-1
gene. Similarly, in patients with PV with 4G/4G and 5G/5G
and the presence of the JAK2V617F mutation revealed the genotypes and in patients with PMF with 4G/4G and
4G/4G, 4G/5G, and 5G/5G genotypes of the PAI-1 gene in 4G/5G genotypes, the C×PLT/RBC index was also higher
ten (22.7 %), twenty two (50.0%), and twelve (27.3%) cases, compared to the control group.
respectively. The detection rate was 4G/5G > 5G/5G > 4G/4G.
In 12 patients without JAK2 mutations, 4G/4G, 4G/5G, and 4. Discussion
5G/5G genotypes occurred in one (8.3%), seven (59.3%),
and four (33.3%) cases, respectively (P > 0.05 compared to In carcinogenesis, disorders in the multifunctional uPA-
carriers of the JAKV617F mutation). The detection rate was uPAR-PAI-1/PAI-2 system, and particularly an increase
4G/5G > 5G/5G > 4G/4G. The 4G allele was detected in in the level of the main uPA inhibitor, PAI-1, are of great
47.7% of patients with the JAK2 mutation and in 37.5% of importance. 13,25 A significant rise in PAI-1 levels was also
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patients without the JAK2 mutation (P > 0.05). found in patients with Ph-negative MPNs. PAI-1 levels
may depend on both the genotype of the −675 4G/5G
3.4. Associations of the PAI-1 4G/5G polymorphism polymorphic locus of its gene and the number of PLT,
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with blood cell count and ICIs which are the main source of PAI-1.
Regarding the potential association of the −675 4G/5G The results of this study reveal that in patients with newly
polymorphism in the PAI-1 gene with the cellular diagnosed Ph-negative MPNs, there were no significant
composition of blood in patients with newly diagnosed differences in the distribution of alleles and genotypes of
Ph-negative MPNs before the initiation of treatment, the −675 4G/5G polymorphic locus of the PAI-1 gene,
significant differences were observed. In patients with either between groups of patients with ET, PV, and PMF,

Volume 3 Issue 2 (2024) 6 doi: 10.36922/gtm.2559