Polycythemia vera disorder

Erythroblasts possess unique characteristics as they undergo differentiation from hematopoietic stem cells. During terminal erythropoiesis, these cells incorporate large amounts of iron in order to generate hemoglobin and ultimately undergo enucleation to become mature red blood cells, ultimately delivering oxygen in the circulation. Thus, erythropoiesis is a finely tuned, multifaceted process requiring numerous properly timed physiological events to maintain efficient production of 2 million red blood cells per second in steady state...

The Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are enduring and well-known conditions. These disorders are characterized by the abnormal growth of one or more hematopoietic cell lineages in the body's stem cells, leading to the enlargement of organs and the manifestation of constitutional symptoms. Numerous studies have provided evidence indicating that the pathogenesis of these diseases involves the dysregulation of the immune system and the presence of chronic inflammation, both of which are significant factors...

INTRODUCTION: Ruxolitinib (RUX) is a Food and Drug Administration-approved Janus Kinase (JAK) inhibitor shown to be effective in improving hypercatabolic symptoms and splenomegaly in patients with myelofibrosis (MF). RUX therapy provides symptomatic benefits for MF patients but is often discontinued for various reasons including worsening cytopenias. Ruxolitinib Discontinuation Syndrome (RDS) involves an acute cytokine-storm rebound phenomenon that can manifest as an acute relapse of symptoms, worsening splenomegaly, respiratory distress, systemic inflammatory response syndrome, or disseminated intravascular coagulopathy...

Red palms syndrome consists of an intense redness on the palms of the hands and, occasionally, the soles of the feet. This infrequent condition may be primary or secondary. The primary forms are either familial or sporadic. They are always benign and do not require treatment. The secondary forms may have a poor prognosis related to the underlying disease, for which early identification and treatment are imperative. Red fingers syndrome is also rare. It manifests as a persistent redness on the fingers or toes pulp...

BACKGROUND: Osteoarthritis (OA) is a progressive degenerative disease with an inflammatory background. Chronic myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by chronic inflammation and a tendency for connective tissue remodeling. AIM: This study aimed to investigate the prevalence and associated risk factors of symptomatic OA (sOA) in MPN patients. PATIENTS AND METHODS: A total of 100 consecutive MPN (39 essential-thrombocythemia, 34 polycythemia-vera, 27 myelofibrosis) patients treated in two community hematologic centers were cross-sectionally evaluated...

Under normal conditions, iron metabolism is carefully regulated to sustain normal cellular functions and the production of hemoglobin in erythroid cells. Perturbation to the erythropoiesis-iron metabolism axis can result in iron imbalances and cause anemias or organ toxicity. Several congenital and acquired diseases associated with abnormal red cell production are characterized by aberrant iron absorption. Several recent studies have shown that improvements in red blood cell production also ameliorate iron metabolism and vice versa...

OBJECTIVE: This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of red blood cell, platelet, and plasma cell disorders. LATEST DEVELOPMENTS: Cerebrovascular complications can occur in patients with blood cell and platelet disorders. Treatment strategies to prevent stroke are available for patients with sickle cell disease, polycythemia vera, and essential thrombocythemia. A diagnosis of thrombotic thrombocytopenic purpura should be considered in patients with neurologic symptoms, hemolytic anemia, thrombocytopenia, mild renal insufficiency, and fever...

RATIONALE: Precapillary pulmonary hypertension (PH) is a rare and largely unrecognized complication of myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF). OBJECTIVES: To describe characteristics and outcomes of MPN-associated PH. METHODS: We report clinical, functional, and hemodynamic characteristics, classification and outcomes of patients with PV, ET or primary MF in the French PH registry...

BACKGROUND: Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) have a higher burden of cardiac calcifications compared to the general population. It is not known whether the JAK2V617F mutation is associated with increased cardiac calcification. AIM: To investigate if a higher JAK2V617F variant allele frequency (VAF) is associated with severe coronary atherosclerosis and the presence of aortic valve calcification (AVC). METHODS: Patients with MPNs were examined by cardiac computer tomography to establish coronary artery calcium score (CACS) and AVC score...

Polypharmacy, potentially inappropriate medications (PIMs), and drug-to-drug interactions (DDIs) are highly prevalent in the elderly and may have adverse effects on health-related outcomes. Their occurrence and clinical and prognostic associations in patients with chronic myeloproliferative neoplasms (MPN) are unknown. We retrospectively evaluated polypharmacy, PIMs, and DDIs in a cohort of 124 MPN patients (essential thrombocythemia, ET = 63, polycythemia vera, PV = 44, myelofibrosis = 9, MPN unclassifiable = 8) from a single community hematology practice...

The regulation of apoptosis (the programmed cell death) is dependent on the crucial involvement of BCL2 and BAX. The Bax-248G>A and Bcl-2-938 C>A polymorphic variations in the promoter sequences of the Bax and Bcl-2 gene have been recently associated with low Bax expression, progression to advanced stages, treatment resistance, and shortened overall survival rate in some hematological malignancies, including chronic myeloid leukemia (CML) and other myeloproliferative neoplasms. Chronic inflammation has been linked to various stages of carcinogenesis wherein pro-inflammatory cytokines play diverse roles in influencing cancer microenvironment leading to cell invasion and cancer progression...

BACKGROUND: Janus kinase 2 (JAK2) V617F gene mutation is an important marker for the diagnosis of Philadelphia negative Myeloproliferative neoplasms (MPN) which is subdivided into Polycythemia Vera (PV), Primary Myelofibrosis (PMF), and Essential Thrombocythemia (ET). The aim here is to investigate the JAK2 allele burden of the patients diagnosed with the subgroups of MPN and to demonstrate the alterations of hematological parameters and spleen size between diagnosis and 6 months of treatment...

BACKGROUND Erythrocytosis results from primary or secondary causes and is characterized by an increased red blood cell count. Secondary erythrocytosis is a result of an underlying cause outside the bone marrow and is often mediated by erythropoietin. Paragangliomas are rare tumors characterized by increased release of catecholamines with symptoms such as hypertension, hematuria, headache, sweating, and post-micturition syncope. Polycythemia-paraganglioma syndrome (PPS) is exceedingly rare, and reports in the literature are limited...

AIMS: Identification of recurrent genetic alterations in JAK2 , MPL and CALR remains crucial in the diagnosis of Philadelphia-negative myeloproliferative neoplasms (MPNs). Current laboratory testing algorithms may entail batching and/or sequential testing, involving multiple testing modalities and sometimes send-out testing that increase the technical and economic demands on laboratories while delaying patient diagnoses. To address this gap, an assay based on PCR and high-resolution melting (HRM) analysis was developed for simultaneous evaluation of JAK2 exons 12-14, MPL exon 10 and CALR exon 9, embodied in the HemeScreen® (hereafter 'HemeScreen') MPN assay...

Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells; these include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPNs are inflammatory cancers, wherein the malignant clone generates cytokines that sustain the inflammatory drive in a self-perpetuating vicious cycle. The course of MPNs follows a biological continuum, that is, from early cancer stages (ET/PV) to advanced myelofibrosis as well as impending leukemic transformation. MPN-related symptoms, e...

The Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2V617F , CALR, or MPL mutations...

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Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e. , polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g. , portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations ( e...

Aberrant activity of Janus kinase 2 (JAK2) is a known driver of several myeloproliferative disorders, including polycythemia vera, and thalassemia. Several inhibitors have been proposed to inhibit JAK2 activity in order to control the disease progression. Ruxolitinib and fedratinib that targets JAK2 kinase have been approved for use in myeloproliferative neoplasms patients. Experimental structures of JAK2 complexed with ruxolitinib provide insights into critical interactions of ruxolitinib. In this work, using a high-throughput virtual screening followed by experimental validations, we have identified a novel natural product from ZINC database that interacts with JAK2 in a manner similar to ruxolitinib and inhibits the activity of JAK2 kinase...

Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell-derived disorders characterized by uncontrolled proliferation of differentiated myeloid cells. Two main groups of MPN, BCR::ABL1 -positive (Chronic Myeloid Leukemia) and BCR::ABL1 -negative (Polycythemia Vera, Essential Thrombocytosis, Primary Myelofibrosis) are distinguished. For many years, cytomorphologic and histologic features were the only proof of MPN and attempted to distinguish the different entities of the subgroup BCR::ABL1 -negative MPN...