The authors describe the first report of a patient being safely transplanted with a liver from a donor who suffered from JAK2V617F mutation-driven essential thrombocythaemia to a patient with a critical burden of hepatocellular carcinoma.
The recent discovery of JAK2 and/or MPL mutations in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has had a major impact on how we diagnose and treat these disorders.
Median mutation levels in pretreatment ET samples were significantly higher for MPL-mutated cases (60%) than for JAK2-mutated cases (24%; P=0.01), as was presentation with anemia.
Although polycythemia vera JAK2V617F and essential thrombocythemiaJAK2V617F shared similarities in localization, distribution, and amount of megakaryocytes, morphology was different.
JAK2 and MPL mutations appear to exert a phenotype-modifying effect and are distinctly associated with polycythemia vera, essential thrombocythemia and primary myelofibrosis; the corresponding mutational frequencies are approximately 99, 55 and 65% for JAK2 and 0, 3 and 10% for MPL mutations.
A point mutation in exon 14 of the JAK2 gene resulting in the formation of the JAK2V617F transcript occurs in 95% of PV patients and around 50% of ET and PMF patients driving constitutive activation of the JAK/STAT pathway.
No increase of JAK2 46/1 haplotype frequency in essential thrombocythemia with CALR mutations: Functional effect of the haplotype limited to allele with JAK2V617F mutation but not CALR mutation.
Description of recurrent genetic abnormalities in driver genes, including Janus Kinase 2 (JAK2), myeloproliferative leukemia and calreticulin, a better appreciation of the key diagnostic role of bone marrow features, results of large epidemiologic studies and a few but landmark controlled clinical trials produced in the last decade, all resulted in a reappraisal of the approach to polycythemia vera and essential thrombocythemia.
This review first considers the factors that may influence phenotype in JAK2-mutated MPNs, especially polycythemia vera (PV) and essential thrombocythemia (ET), and then discusses the mutations implicated in JAK2-negative MPNs such as in MPL and epigenetic regulators.
Chronic myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells, which fall into distinct categories based on a number of characteristics including the presence of the BCR-ABL1 gene fusion (chronic myelogenous leukemia) or the JAK2(V617F) mutation (polycythemia vera, primary myelofibrosis, and essential thrombocythemia).
As compared with patients in whom the TET2 mutation was acquired first (hereafter referred to as "TET2-first patients"), patients in whom the Janus kinase 2 (JAK2) mutation was acquired first ("JAK2-first patients") had a greater likelihood of presenting with polycythemia vera than with essential thrombocythemia, an increased risk of thrombosis, and an increased sensitivity of JAK2-mutant progenitors to ruxolitinib in vitro.
These findings suggest that the JAK2V617F mutation is not rare in childhood sporadic ET cases, and that these cases might be older and myeloproliferative features.
The current study describes rare cases of SAH accompanied by ischemic stroke secondary to ET along with a review of the current literature, implying specific mechanisms for cerebral artery disorders associated with JAK2V617F mutation.
Different numbers of cell lineages harboring the JAK2-V617F mutation were found, being the lowest in ET (17/30), higher in PV (24/30) and in PMF (22/30).
Aspirin-responsive, migraine-like transient cerebral and ocular ischemic attacks and erythromelalgia in JAK2-positive essential thrombocythemia and polycythemia vera.
Accordingly, the WHO concept of two distinct entities, ET and prefibrotic IMF, does not seem to fit the model of JAK2-positive ET as part of a biological continuum of JAK2V617F-positive chronic myeloproliferative disorders.
This indicates that JAK2 V617-positive ET patients, diagnosed according to the PVSG criteria, represent a "forme fruste of PV" consistent with early PV mimicking ET (JAK2V617F trilinear MPD).
An activating JAK2 mutation (JAK2V617F) is present in the chronic myeloproliferative disorders (MPDs), polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocytosis (ET).
Among these genetic variations, Philadelphia-negative gain-of-function mutation in the janus kinase 2 (JAK2) protein leads to overexpression of the genes involved in cell growth and proliferation, and has been linked to development of hematological malignancies, specifically, myeloproliferative neoplasms (MPNs; essential thrombocythemia [ET], polycythemia vera [PV], and primary myelofibrosis).
Because of the low incidence of JAK2 mutation in acute myeloid leukemia (AML), the clinical features of AML with JAK2 mutation are rarely reported so far, either transformed from essential thrombocythemia (ET) or de novo AML.
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients.
The JAK2(V617F) mutation is present in the majority of patients with polycythemia vera and one-half of those with essential thrombocythemia and primary myelofibrosis.