Approximately 6% and 14% of JAK2V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients, respectively, have 'canonical' MPL exon 10 driver mutations W515L/K/R/A or S505N, which generate constitutively active receptors and consequent loss of Tpo dependence.
Somatic mutations of calreticulin (CALR) have been described in approximately 60-80% of JAK2 and MPL unmutated Essential Thrombocythemia and Primary Myelofibrosis patients.
To make a definite diagnosis of essential thrombocytosis (ET) from reactive thrombocytosis (RT), the most reliable criteria are the presence of driver mutations, namely JAK2, CALR, or MPL gene mutations.
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.
The Janus kinase 2 (<i>JAK2</i>) V617F mutation is common in patients with breakpoint cluster region-Abelson1 (<i>BCR-ABL1</i>)-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis, but is rarely detected in <i>BCR-ABL1-</i>positive chronic myeloid leukemia (CML) patients.
One hundred five Philadelphia-negative MPN patients, including polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF) were initially screened for JAK2 mutations by amplification-refractory mutation system (ARMS-PCR) methodology and were further subjected to detection of CALR gene mutations by our in-house assay, a PCR based amplicon length differentiation assay (PCR-ALDA).
Subsequently, the patient was diagnosed with ET because the platelet count gradually increased to 50.0×10<sup>4</sup>/μL, and <i>JAK2 V617F</i> mutation was identified.
Calreticulin (CALR) exon 9 frameshift mutations have recently been identified in 30-40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) without JAK2 or MPL mutations.
A 70-year-old woman with a five-year history of ET with JAK2V617F mutation treated with hydroxycarbamide for five months presented with petechiae on her limbs.
In essential thrombocythaemia (ET), the patients with the JAK2V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy.
The V617F mutation in the JH2 domain of JAK2 is an oncogenic driver in several myeloproliferative neoplasms (MPNs), including essential thrombocythemia, myelofibrosis, and polycythemia vera (PV).
However, for essential thrombocythemia (ET), female gender or JAK2 positive, there is a significant increased risk to those carrying at least one variant allele for CASP9.
Compared to JAK2-mutated ET patients, CALR-mutated ET patients were younger, showed lower WBC counts, lower hemoglobin levels, higher platelet counts, and fewer thrombotic events.
Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis.