Editorial Volume 3 Issue 4 - December 2018 DOI: 10.19080/JTMP.2018.03.555620 J Tumor Med Prev Copyright © All rights are reserved by Nahla AM Hamed Polycythemia Vera: Current Therapeutic Approaches Nahla AM Hamed* Department of Hematology, Faculty of Medicine, Alexandria University, Egypt Submission: November 05, 2018; Published: December 07, 2018 *Corresponding author: Nahla AM Hamed, Department of Hematology, Faculty of Medicine, Alexandria University, Egypt Introduction PV is one of the lower-risk subtypes of MPNs [1] that is characterized primarily by clonal erythrocytosis [2]. It has an annual incidence of 0.21-2.27 per 100,000. Median age at diagnosis is estimated at 71 years. A male preponderance is noted. JAK2 V617F is found in >95% of PV patients and JAK2 exon 12 mutations in ~4% [3]. JAK2 exon 12 mutations such as insertions or deletions are relatively specific to JAK2V617F-negative PV and not found in ET and PMF [4]. JAK2 homozygosity is neither necessary nor sufficient for a PV phenotype as indicated by presence of small or undetectable homozygous clones in some PV patients [5]. Heterozygous mutant erythroblasts of PV patients have distinct transcriptional profiles that precede acquisition of homozygosity and reflect differential activation of phosphorylated STAT1, which modulate erythropoiesis [5]. CALR and MPL have distribution frequency of 0 and 0% [6]. Other mutations (e.g., LNK) have been reported [2]. Co-occurrence of CALR mutation exon 9 with JAK2V617F, usually occurs in less than 1% of PV [4]. JAK2, MPL, and calreticulin mutations are driver mutations that activate the JAK2 pathway, but additional recurrent somatic mutations in several genes (TET2, ASXL1, DNMT3A, CBL, LNK, IDH1/2, IKF1, EZH2, TP53, and SRSF2), encoding transcriptional and epigenetic regulators and signaling proteins, modulate disease progression and can also occur as a primary mutation [3]. Clinical features of PV include mild-to moderate degree of splenomegaly, mild-to-moderate degree of constitutional symptoms, including fatigue and pruritus [6] (usually after bathing) [2], symptoms of hyperviscosity, leukocytosis, thrombocytosis, microvascular symptoms (e.g., headaches, lightheadedness, visual disturbances [6] e.g., blurry vision [2], atypical chest pain, acral paresthesia and erythromelalgia [6] i.e., erythema, warmth, and pain in distal extremities) [2], and thrombotic and bleeding complications [6]. The risk of thrombosis exceeds 20% [7]. History of hypertension predicted arterial thrombosis and advanced age venous thrombosis [7]. Hepatic and portal vein thrombosis is a well-recognized phenotypic association with JAK2 V617F and is often observed in younger women, with either a masked phenotype, or lower leukocyte counts and lower allelic burdens. The affected patients present a unique exception with regard to demographics, clinical phenotype, and allelic burden [8]. Some patients may develop AvWS, especially in the presence of extreme thrombocytosis (platelets >1000 x 10 9 /L) and are at risk for aspirin associated bleeding [7]. JAK2 oncogenes homozygosity may result in distinct tumorigenic consequences, but direct evidence has been elusive (5). JAK2V617F homozygosity was associated with reduced platelet survival that is likely to reflect increased platelet apoptosis and/or clearance. Moreover, homozygosity results in reduced platelets numbers, consistent with the lower platelet levels seen in PV compared with ET [5]. Increased JAK2V617F signaling may enhance (or reduce) platelet reactivity, a concept that may be relevant to thrombotic (or hemorrhagic) complications in PV patients [5]. JAK2 V617F homozygous allele burden has been associated with older age, male sex, pruritus, and splenomegaly; associations between homozygous or increasing allelic burdens and thrombosis J Tumor Med Prev 3(4): JTMP.MS.ID.555620 (2018) 0068 Abstract The hemoglobin level threshold required to diagnose PV is now established at 16.5 g/dL for men and 16 g/dL for women by the 2016 WHO classification for MPNs. The clinical course of PV might be interrupted by thrombohemorrhagic complications and disease transformation to MF or acute myeloid leukemia. JAK2 oncogenes homozygosity may result in distinct tumorigenic consequences. Different therapeutic strategies and good candidates’ patients for such therapies are illustrated. Keywords: Polycythemia vera; Thrombohemorrhagic; Tumorigenic; Myeloid leukemia Abbreviations: PV: Polycythemia Vera; STAT: Signal Transducer and Activator of Transcription; AML: Acute myeloid leukemia; MF: Myelofibrosis; MPNs: Myeloproliferative neoplasms