Elevated levels of mast cells are involved in pruritus associated with polycythemia vera in JAK2V617F transgenic mice.

Pruritus Associated with Polycythemia Vera Elevated Levels of Mast Cells Are Involved in

Distinct roles for long-term hematopoietic stem cells and erythroid precursor cells in a murine model of Jak2V617F-mediated polycythemia vera.

In the current model of the pathogenesis of polycythemia vera (PV), the JAK2V617F mutation arises in hematopoietic stem cells (HSCs) that maintain the disease, while erythroid precursor populations expand, resulting in excessive red blood cell production. We examined the role of these specific cell populations using a conditional Jak2V617F knockin murine model. We demonstrate that the most imma...

ارزیابی میزان جهش JAK2V617F در بیماران میلو پرولیفراتیو مزمن به روش AS-RT-PCR

Background and Aim: The JAK2 is an acquired mutation that is observed in majority of patients with classical Philadelphia-negative Myeloproliferative neoplasms that include polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). This acquired mutation is characterized by a G to T transversion at nucleotide 1849 in exon 12 of the JAK2 gene, leading to a substitution ...

Differential NOD/SCID mouse engraftment of peripheral blood CD34+ cells and JAK2V617F clones from patients with myeloproliferative neoplasms.

We evaluated the NOD/SCID engraftment of CD34(+) cells from polycythemia vera (PV) and secondary polycythemia patients (SP) and the JAK2V617F clone before and after transplantation. Peripheral blood CD34(+) cells were transplanted intra-femorally. In the injected BM, successful engraftment (>0.1%) occurred in 8/26 mice transplanted with CD34+ cells from 5/13 PV patients (median: 4.26%, range: 0...

Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.

Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing JAK2 inhibition as a potential therapeutic strategy. Although most polycythemia vera patients carry the JAK2V617F mutation, half of those with essential thrombocythemia or primary myelofibrosis do not, suggesting alternative mechanisms fo...