Phenotype transformation to polycythemia was proven to be possible within the group of JAK2-mutated ET; however, cause of this effect remains uncertain.
To test this, C57BL/6J chow-fed mice received either chronic intraperitoneal (ip) or repeated intracerebroventricular (icv) administration of the selective Jak2 inhibitor NVP-BSK805, which was proven efficacious in treating polycythemia in rodents.
Investigation for polycythaemia and thrombocytosis showed JAK2 positive myeloproliferative neoplasm.A diagnosis of AOP infarction is often missed or delayed because it is rare and presents with variable neurological symptoms.
This observation contrasts with a report suggesting that polycythemia in VHL R200W and H191D homozygotes is due to the loss of JAK2 regulation from VHL R200W and H191D binding to SOCS1.
JAK2(V617F) failed to induce polycythemia in recipients after deletion of Stat5a/b, although the loss of STAT5 did not prevent the development of myelofibrosis.
The JAK2(V617F) mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria.
Nested high-resolution melting curve analysis a highly sensitive, reliable, and simple method for detection of JAK2 exon 12 mutations--clinical relevance in the monitoring of polycythemia.
The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis.
At the forefront are the mutually exclusive exon 14 (JAK2V617F) and exon 12 JAK2 mutations that are almost always present in PV but not in polycythemias of other causes.
The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera.
This work demonstrates that JAK2(V617F) is sufficient for polycythemia and fibrosis development and offers an in vivo model to assess novel therapeutic approaches for JAK2(V617F)-positive pathologies.
Functional analysis demonstrates that this mutation confers erythropoietin-independent growth in vitro, deregulates signaling pathways downstream of JAK2, and causes polycythemia in mice.