When stratified by disease subtypes, the <i>JAK2</i> 46/1 haplotype and <i>JAK2</i> rs12339666 were significantly associated with all three MPN subtypes, but <i>TERT</i> rs2736100 was only associated with essential thrombocythemia and polycythemia vera.
One harbored a 33 bp duplication in exon 12 along with an exon 14 p.V617F mutation, another had an exon 12 p.H538_K539delinsL, and a third carried a previously unreported mutation in PV, p.L611S, alone, and in cis with p.V617F.
Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF.
Three additional JAK2 SNPs (rs10758669, rs3808850, and rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with ET or PMF.
Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF.
Three additional JAK2 SNPs (rs10758669, rs3808850, and rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with ET or PMF.
Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF.
The V617F mutation in the JH2 domain of JAK2 is an oncogenic driver in several myeloproliferative neoplasms (MPNs), including essential thrombocythemia, myelofibrosis, and polycythemia vera (PV).
In the absence of BCR-ABL, the conventional diagnostic algorithm recommends JAK2 V617F mutation testing to support diagnosis of other MPN diseases such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
The advances in molecular insights, especially the discovery of the Janus kinase 2 (JAK2) V617F mutation and its role in JAK-STAT pathway dysregulation, led to the development of the JAK inhibitor ruxolitinib, which currently represents the cornerstone of medical therapy in MF and hydroxyurea-resistant/intolerant PV.
IPF analysis was performed on 22 patients with known JAK2 V617F mutation and 41 patients who were negative for this mutation previously tested because of suspicion of PV.
Moreover, leukocytes > 18 × 10<sup>9</sup>/L and V617F burden allele > 25.7% were statistically significantly different in PV</span> patients (P = .019 and borderline significant at P = .055, respectively), while in ET patients leukocytes > 9.2 × 10<sup>9</sup>/L (P < .001) and age at diagnosis of > 55 years were statistically significantly different (P = .002).
The Janus kinase 2 (<i>JAK2</i>) V617F mutation is common in patients with breakpoint cluster region-Abelson1 (<i>BCR-ABL1</i>)-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis, but is rarely detected in <i>BCR-ABL1-</i>positive chronic myeloid leukemia (CML) patients.
The results suggested that plasma Dkk-1 levels could differentiate ET from pre-PMF, in JAK2 V617F-positive as well as in CALR-positive patients, and also ET from PV in JAK2 V617F-positive patients.
Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95%, 90.5%, and 9.1%, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively.
A point mutation in exon 14 of the JAK2 gene resulting in the formation of the JAK2 V617F transcript occurs in 95% of PV patients and around 50% of ET and PMF patients driving constitutive activation of the JAK/STAT pathway.
However, when a patient presents with isolated thrombocytosis and a positive JAK2 V617F assay, particularly a young woman, the possibility of PV must always be considered because of plasma volume expansion.
The JAK2 V617F mutation was positive before and after the diagnosis of PV; however, new chromosomal abnormalities were detected during the progression.