Our studies correlating the frequency of JAK2(V617F) mutant allele and clonality, as well as the presence of homozygous wild-type JAK2 erythropoietin-independent erythroid colonies, provide compelling evidence that the JAK2(V617F) is not the PV-initiating mutation.
Therefore, in a patient with acquired erythrocytosis, it is reasonable to begin the diagnostic work-up with peripheral blood JAK2 mutation analysis and serum Epo measurement to distinguish PV from secondary erythrocytosis.
Human erythroid malignancies (polycythemia vera [PV] and erythroleukemia) are associated with erythropoietin (Epo)-independent growth and differentiation.
Therefore, a contemporary approach to the diagnosis of polycythemia vera starts with peripheral blood mutation screening for JAK2(V617F) as well as measurement of serum erythropoietin.
Adding low EPO or the JAK2 V617F allele burden did not improve the diagnostic accuracy for PV whereas the inclusion of both improved the sensitivity up to 83% and maintaining 96% specificity.
We have undertaken a study designed to determine whether a mutation in the Epo receptor (Epo-R) gene could cause the polycythemia phenotype seen in either dominant or recessive primary polycythemia described by us and others, or in polycythemia vera.
The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera.
Differently from polycythemia vera, EPOR G1251T CD34(+) cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO.
As compared to their JAK2 V617F negative counterparts, the JAK2 V617F positive patients had PV-like biochemical characteristics such as higher haemoglobin levels (p=0.02), lower platelet counts (p=0.002) and lower plasma EPO levels (p=0.04).
Clinically suspected PV with low serum erythropoietin and absent JAK2(V617F), together with the bone marrow findings of erythroid hyperplasia and subtle megakaryocytic atypia, should prompt an evaluation for an exon 12 mutation.
Normally, erythropoietin is essential for the survival and proliferation of erythroid progenitors; however in polycythemia vera the erythroid progenitor cells can survive and develop in the absence of erythropoietin.
Furthermore, deletion of Stat5 completely abrogated erythropoietin (Epo)-independent erythroid colony formation evoked by Jak2V617F, a hallmark feature of PV.
Conversely, exposure of polycythemia vera CD34(+) cells to small interfering RNA against pre-miR-16-2 reduced erythroid colonies and largely prevented formation of erythropoietin-independent colonies; myeloid progenitors remained unaffected.
Characteristic features of PV are erythropoietin (Epo)-independent in vitro erythroid colony formation, as well as hypersensitivity to many other hematopoietic growth factors.
The biologic hallmark of polycythemia vera (PV) is the formation of endogenous erythroid colonies (EECs) with an erythropoietin-independent differentiation.
Furthermore, CYT387 selectively suppressed the in vitro growth of erythroid colonies harboring JAK2V617F from polycythemia vera (PV) patients, an effect that was attenuated by exogenous erythropoietin.
Deregulated erythropoiesis in PV involves EPO hypersensitivity and apoptosis resistance of erythroid precursor cells associated with abnormally increased activation of RAS-ERK and phosphoinositide-3 kinase-AKT pathways.
Screening a cohort of 10 idiopathic erythrocytosis, 28 polycythemia vera, and 7 secondary erythrocytosis cases allowed the detection of 15 mutants, including 9 different mutations, of which 3 were unreported, all in the polycythemia vera group, and presented a characteristic profile: pure erythrocytosis associated with low serum erythropoietin.
To search for EPO-receptor changes as a possible pathophysiologic mechanism, we examined, by Southern blot analysis, genomic DNA samples from affected and nonaffected family members, as well as three patients with PV.
A diagnosis of polycythemia vera (PV) was made after investigation revealed a low erythropoietin and elevated leukocyte alkaline phosphatase (LAP) score; he was treated with repeated phlebotomies.
We evaluated the presence of the Jak2V617F mutation and increased PRV-1 mRNA expression along with previously established markers - erythropoietin (EPO) independent colony formation (EEC) and erythropoietin level for diagnosis of PV and assessment of treatment efficiency.
Polycythaemia vera (PV) is a myeloproliferative disorder characterized by haematopoietic progenitor cells being hypersensitive to cytokines such as erythropoietin, interleukin-3, stem cell factor and insulin-like growth factor 1, which results in an increased production of mature blood cells.