Germline Genetic Factors Affecting Interferon Alpha Therapy in Polycythemia Vera

Evidence for Superior Efficacy and Disease Modification after Three Years of Prospective Randomized Controlled Treatment of Polycythemia Vera Patients with Ropeginterferon Alfa-2b Vs. HU/BAT

The Impact of Myeloproliferative Neoplasms (MPNs) on Patients' Quality of Life and Productivity: Results from the International MPN Landmark Survey

Detection of the Single Hotspot Mutation in the JH2 Pseudokinase Domain of Janus Kinase 2 in Bone Marrow Trephine Biopsies Derived from Chronic Myeloproliferative Disorders

Introduction Polycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm (MPN). A newly developed PV treatment option, ropeginterferon alfa-2b, contains recombinant human alfa monoisomer as an active ingredient, resulting in a novel pharmacologic profile and improved tolerability. Efficacy studies conclude remarkable long-term hematological response and sustained JAK2V617F allele burden reduction. Ropeginterferon alfa-2b compound has been approved for the treatment of polycythemia vera without symptomatic splenomegaly. Areas covered Current clinical trials are investigating the role of ropeginterferon alfa-2b in the first-line setting of treatment for PV. The safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues are also discussed of ropeginterferon alfa-2b. Expert opinion Ropeginterferon alfa-2b is a targeted therapeutic option in the treatment of PV, representing a significant improvement compared to conventional cytoreductive therapies. The single isomer entity of the recombinant human interferon alfa-2b and the mono-pegylation method imparts favorable properties to the compound. The use of ropeginterferon alfa-2b allows extended dosing interval, reduces side effects, and may increase the overall survival of PV patients by reducing the risk of progression to myelofibrosis or acute leukemia. Clinical data suggests that the compound may provide a disease-modifying option for PV patients with asymptomatic splenomegaly.

Gene Expression Profiling Distinguishes Essential Thrombocythemia from Polycythemia Vera Patients and Identifies a Common Expressed Set of Genes in Relation to JAK2V617F Status

JAK2 Gene Is Mutated in Patients with Myeloproliferative Disorders and Spontaneous Erythroid Colony Formation but Not in Patients with Spontaneous Megakaryocyte Growth Only.

The expression of Death Inducer-Obliterator (DIDO) variants in Myeloproliferative Neoplasms

Polycythemia vera erythroid precursors exhibit increased proliferation and apoptosis resistance associated with abnormal RAS and PI3K pathway activation

561 Renin-angiotensin system expression in myeloproliferative diseases

Survival Patterns in Patients with Non-CML Myeloproliferative Neoplasms: Evidence From a United States SEER/Medicare Population

low-risk PV patients with arterial hypertension represent a subgroup in which a more intensive therapy should be explored in prospective studies designed to examine whether the addition of cytoreductive drugs to phlebotomy and aspirin and ACE inhibitors may reduce the still high incidence of thrombosis.

Polycythemia vera (PV) is a clonal myeloproliferative neoplasms (MPN) deriving from hematopoietic stem cells (HSC), with a median survival of about 14 years. Thrombosis is the major complication affecting the survival of PV patients as well as the most common cause of death in PV patients. For PV patients, thrombosis is the result of the combined effects of various factors, and its pathogenesis is very complicated. There are many factors affecting the incidence of thrombosis in PV patients, including age, history of thrombosis, count of blood cells, platelet activity, treatment modality, JAK2 V617F burden. This paper reviews the factors affecting thrombosis in PV patients. Key words: Polycythemia vera; Thrombosis; Influential factors

Platelet Adhesion Under Flow Condition in Patients with Essential Thrombocythemia (ET) and Polycythemia Vera (PV): Analysis According to the Mutational Status

Myeloproliferative neoplasms (MPNs) constitute a group of phenotypically diverse chronic myeloid malignancies, characterized by clonal hematopoiesis and excessive production of terminally differentiated myeloid blood cells. The MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), most of which are characterized by a somatic point mutation, V617F, in the janus kinase 2 (JAK2) gene. This mutation was recently shown to occur more frequently in a specific JAK2 haplotype, JAK2 46/1, in North American and European MPN patients. Little is known, however, about JAK2 haplotypes in Japanese MPN patients. Therefore, we examined 108 Japanese patients with MPN, including 19 with PV, 61 with ET, 10 with PMF, and 17 with unclassifiable MPN, as well as 104 control individuals for the JAK2 rs10974944(C/G) single nucleotide polymorphism, in which the G allele indicates the 46/1 haplotype. We found that the JAK2 46/1 haplotype was significantly more frequent in patients with V617F-positive MPN than in controls (odds ratio [OR], 3.6; 95 % confidence interval [CI], 2.2-5.8, p < 0.001), and in PV patients than in controls (OR, 6.3; 95 % CI, 3.0-29.4, p < 0.001). In conclusion, we demonstrated that the JAK2 46/1 haplotype is associated with JAK2 V617F-positive MPNs in Japanese patients.

Single Center Experience with Screening for JAK2 V617F, cMPL W515L, cMPL W515K, and JAK2 L611V Mutations in MPN. Rarity of JAK2 L611V Does Not Justify Its Routine Screening