TET2 rs1548483 SNP Associating with Susceptibility to Molecularly Annotated Polycythemia Vera and Primary Myelofibrosis

Lighezan, Diana L.; Bojan, Anca; Iancu, Mihaela; Pop, Raluca Maria; Gligor-Popa, Ștefana; Tripon, Florin; Cosma, Adriana S; Tomuleasa, Ciprian; Dima, Delia; Zdrenghea, Dumitru; Fetică, Bogdan; Ioniță, Ioana; Gaál, Ildikó O.; Vișan, Simona; Mirea, Andreea-Manuela; Popp, Radu A.; Florea, Mira; Araniciu, Cătălin; Petrescu, Lucian; Pop, Ioan Victor; Bănescu, Claudia

doi:10.3390/jpm10040259

Cited by 8 publications

(10 citation statements)

References 40 publications

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“…According to the WHO classification, the PMF cohort includes prefibrotic myelofibrosis and overt myelofibrosis. We show that PMF subjects with the rs3025039 minor T-allele have an increased susceptibility to the JAK2 V617F driver mutation, in keeping with data indicating that other genetic polymorphisms in JAK2, MECOM, TERT, TET2, HBS1L-MYB, and the corticosteroid receptor predispose to acquiring JAK2 V617F [26][27][28][29][30][31][32][33].…”

Section: Discussionsupporting

confidence: 88%

Clinical Relevance of VEGFA (rs3025039) +936 C>T Polymorphism in Primary Myelofibrosis: Susceptibility, Clinical Co-Variates, and Outcomes

Villani¹,

Carolei²,

Rosti³

et al. 2021

Genes

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We evaluated the association of VEGFA rs3025039 polymorphism with clinical co-variates and outcomes in 849 subjects with primary myelofibrosis (PMF) and 250 healthy controls. Minor T-allele frequency was higher in subjects with JAK2V617F compared with those without JAK2V617F (18% vs. 13%; p = 0.014). In subjects with JAK2V617F, the TT genotype was associated at diagnosis with lower platelet concentrations (p = 0.033), higher plasma LDH concentration (p = 0.005), higher blood CD34-positive cells (p = 0.027), lower plasma cholesterol concentration (p = 0.046), and higher concentration of high-sensitivity C-reactive protein (p = 0.018). These associations were not found in subjects with PMF without JAK2V617F. In subjects with the TT genotype, risk of death was higher compared with subjects with CC/CT genotypes (HR = 2.12 [1.03, 4.35], p = 0.041). Finally, the TT genotype was associated with higher frequency of deep vein thrombosis in typical sites (12.5% vs. 2.5%; OR = 5.46 [1.51, 19.7], p = 0.009). In conclusion, in subjects with PMF, the VEGFA rs3025039 CT or TT genotypes are more common in those with JAK2V617F than in those without JAK2V67F mutation and are associated with disease severity, poor prognosis, and risk of deep vein thrombosis.

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Section: Discussionsupporting

confidence: 88%

Clinical Relevance of VEGFA (rs3025039) +936 C>T Polymorphism in Primary Myelofibrosis: Susceptibility, Clinical Co-Variates, and Outcomes

Villani¹,

Carolei²,

Rosti³

et al. 2021

Genes

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“…The high frequency of the G allele of rs10974944 in individuals positive for JAK2 V617F contributes to discussions about the non-random correlation between these two genetic alterations 13,40 This relationship is in line with another nding from our study, haplotype 2 (rs10974944G/rs10815151C/rs1011004A/rs77375493T), which strengthens concepts based on the interaction between rs10974944 (C > G) and JAK2 V617F (rs77375493 -G > T). These propositions are in agreement with ndings involving haplotype 46/1 in other Brazilian, Taiwanese, European, Chinese, and Japanese populations 16,[32][33][34]41 , indicating that the possible mechanisms preceding the acquisition of JAK2 V617F are not limited to a speci c ethnic group; therefore, its evolutionary basis can be considered as a genetic predisposition factor for the disease 8 .…”

Section: Discussionsupporting

confidence: 89%

Hematological alterations associated with the SNV rs10974944, part of the 46/1 haplotype, in patients from the Brazilian Amazon with BCR::ABL1-negative myeloproliferative neoplasms

Paes,

Torres,

Aquino

et al. 2024

Preprint

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BCR::ABL1-negative myeloproliferative neoplasms are hematopoietic disorders characterized by panmyelosis. JAK2 V617F is a frequent variant in these diseases and often occurs in the 46/1 haplotype. The G allele of rs10974944 has been shown to be associated with this variant, specifically its acquisition, correlations with familial cases, and laboratory alterations. This study evaluated the association between the 46/1 haplotype of JAK2 in patients with myeloproliferative neoplasms in a population from the Brazilian Amazon. Clinical, laboratory and molecular sequencing analyses were considered. Carriers of the G allele of rs10974944 with polycythemia vera showed an increase in mean corpuscular volume and mean corpuscular hemoglobin, while in those with essential thrombocythemia, there was an elevation in red blood cells, hematocrit, and hemoglobin. Associations were observed between rs10974944and the JAK2 V617F, in which the G allele (OR: 3.47; p < 0.0001), CG genotype (OR: 8.4; p = 0.002), and GG genotype (OR: 4.1; p = 0.002) were associated with JAK2 V617F+ and an increase in variant allele frequency (GG: OR 13.1; p = 0.004; G: OR: 6.0; p = 0.0002). These results suggest an association between rs10974944 (G) and a status for JAK2 V617F, JAK2 V617F+_VAF ≥50%, and laboratory alterations in the erythroid lineage.

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“…This justifies the higher frequency of CALR mutation in CMD-IT and explains its milder disease phenotype [21][22][23][24]. Since a high number of gene variations have been associated with PMF susceptibility, these data open new perspectives on our understanding of the relationship between genetic susceptibility and MPN diversity [25][26][27][28].…”

Section: Discussionmentioning

confidence: 87%

Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype

Barosi¹,

Campanelli²,

Massa³

et al. 2022

Acta Haematol

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Introduction: About 15% of people with a myeloproliferative neoplasm (MPN) are identified as MPN, unclassifiable using the 2016 WHO classification. Methods: We tested whether persons with platelet concentration ≥450 × 10E+9/L, bone marrow megakaryocyte morphology typical of prefibrotic/early myelofibrosis (pre-MF), and no minor criteria of pre-MF should be classified as a distinct MPN subtype, clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). Results: 139 subjects meet these criteria who we compared with primary myelofibrosis (PMF) including 402 with pre-MF and 521 with overt myelofibrosis. CMD-IT subjects were more likely female and younger. They had lower frequencies of JAK2V617F compared with persons with PMF (55% vs. 70%; p < 0.001) and higher frequencies of CALR mutations (37% vs. 17%; p < 0.001). They also had lower frequency of variations associated with JAK2V617F susceptibility, JAK2 46/1 (35% vs. 47%; p = 0.021), and VEGFA rs3025039 (12% vs. 17%; p = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; p < 0.001) and longer survival (median, not reached vs. 23 years; HR = 0.34 (0.10, 0.30); p < 0.001). Conclusion: Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms.

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TET2 rs1548483 SNP Associating with Susceptibility to Molecularly Annotated Polycythemia Vera and Primary Myelofibrosis

Cited by 8 publications

References 40 publications

Clinical Relevance of VEGFA (rs3025039) +936 C>T Polymorphism in Primary Myelofibrosis: Susceptibility, Clinical Co-Variates, and Outcomes

Clinical Relevance of VEGFA (rs3025039) +936 C>T Polymorphism in Primary Myelofibrosis: Susceptibility, Clinical Co-Variates, and Outcomes

Hematological alterations associated with the SNV rs10974944, part of the 46/1 haplotype, in patients from the Brazilian Amazon with BCR::ABL1-negative myeloproliferative neoplasms

Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype

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