Understanding the Molecular Pathophysiology of Polycythemia Vera

Understanding the Molecular Pathophysiology of Polycythemia Vera


Understanding the molecular
pathophysiology of polycythemia vera polycythemia vera or PV is a
myeloproliferative neoplasm characterized primarily by
erythrocytosis which is a serious pathology linked to an increased risk of
thrombosis and substantial symptom burden PV occurs most often in older
people in fact the mean age at PV diagnosis is about 60 years and
incidence increases with age many patients affected by PV are
asymptomatic others may have symptoms that are not unique to PV oftentimes the
diagnosis of PV is first considered in patients who present with a high
hemoglobin level more than 18.5 grams per deciliter in men
and more than 16.5 grams per deciliter in women adherence to updated
diagnostic criteria established in 2008 by the World Health Organization may
help to facilitate a PV diagnosis at present the precise etiology of PV
remains unknown however dysregulated signaling in the
Janus kinase or JAK pathway plays a role in its pathogenesis normal JAK pathway
signaling begins when a cytokine where growth factor the ligand binds to a
receptor on blood forming cells ligand binding induces a series of steps
including receptor dimerization and the activation of JAK and stat proteins via
phosphorylation activated stats dimerize and move from the cytoplasm into the
nucleus once there they ultimately control the transcription of various
downstream genes dysregulated JAK signaling can occur through many
mechanisms the JAK2V617F mutation is detected in about 95 percent of
patients with PV that tattoo mutation and the JAK2 exon 12 mutation are
detected in about 16 percent and 3 percent of patients with PV respectively
although rare other mutations including IDH1 IDH2, MPL exon 10 , and CBL exons 8, 9 have also been identified in PV Risk stratification in PV is based mainly on
prognostic indicators of thrombotic risk risk of cardiovascular complications
from PV has been shown to be greatest in patients older than age 65 years and in
those with a history of thrombosis leukocytosis has been shown to be an
independent risk factor for thrombosis and survival in PV the main goal of PV
treatment is to consistently maintain the hematocrit level below 45% to avoid
thrombotic events and bleeding complications PV is a serious disease
that affects primarily older people further research to identify new
therapeutic strategies is clearly needed At Incyte we believe a better
understanding of the mechanisms of cancer and inflammation will deliver
better patient outcomes

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