These results demonstrate that STAT5a/b is essential for the induction of CML-like leukemia by BCR-ABL1 and of polycythemia by JAK2(V617F), and validate STAT5a/b and the genes they regulate as targets for therapy in these MPNs.
We attribute the reversal of erythrocytosis/polycythemia to translational repression of Hif2α expression by Tempol-mediated increases in the IRE-binding activity of Irp1, as reversal of polycythemia was abrogated in VhlR200W mice in which Irp1 was genetically ablated.
Irp1(-/-) mice develop polycythemia and pulmonary hypertension, and when these mice are challenged with a low iron diet, they die early of abdominal hemorrhages, suggesting that Irp1 plays an essential role in erythropoiesis and in the pulmonary and cardiovascular systems.
On the other hand, the frequency of neonatal complications showed higher tendency of neonatal complications in the incidence of polycythaemia ( P = 0.094) and heavy-for-date ( P = 0.071) in the glycated albumin ⩾15.8% group compared with the glycated albumin <15.8 group.
Ligand-induced EpoR internalization is mediated by JAK2 and p85 and is impaired by mutations responsible for primary familial and congenital polycythemia.
Conversely, the patient with life-long erythrocytosis is more likely to suffer from congenital polycythemia and should therefore be evaluated for germline mutations that result in enhanced Epo effect (for example, Epo receptor mutations), altered intracellular oxygen sensing (for example, mutations involving the von Hippel-Lindau tumor suppressor gene) or decreased P50 (for example, high-oxygen-affinity hemoglobinopathy).
Conversely, the patient with life-long erythrocytosis is more likely to suffer from congenital polycythemia and should therefore be evaluated for germline mutations that result in enhanced Epo effect (for example, Epo receptor mutations), altered intracellular oxygen sensing (for example, mutations involving the von Hippel-Lindau tumor suppressor gene) or decreased P50 (for example, high-oxygen-affinity hemoglobinopathy).
In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS).
Exon 12 of ASXL1 was amplified from neutrophil genomic DNA and bidirectionally sequenced in 77 patients with myelofibrosis (including patients with primary and post-essential thrombocytosis or post-polycythemia myelofibrosis), 42 patients with polycythemia vera, 41 with essential thrombocytosis and 6 with post-myelofibrosis acute myeloid leukemia.
Early down-regulation of Bcl-xL expression during megakaryocytic differentiation of thrombopoietin-induced CD34+ bone marrow cells in essential thrombocythemia.
These results demonstrate that STAT5a/b is essential for the induction of CML-like leukemia by BCR-ABL1 and of polycythemia by JAK2(V617F), and validate STAT5a/b and the genes they regulate as targets for therapy in these MPNs.
In addition to erythrocytosis, the BGN <sup>Tg</sup> mice showed elevated hemoglobin concentrations, hematocrit values and enhanced total iron binding capacity, revealing a clinical picture of polycythemia.
Ligand-induced EpoR internalization is mediated by JAK2 and p85 and is impaired by mutations responsible for primary familial and congenital polycythemia.
Beyond this, when C-terminal truncated hEPOR-T mutant alleles as harbored by polycythemia patients are co-expressed with the wild-type EPOR in EPO-dependent erythroid progenitors, several specific events become altered.
The 5 TCAs were used to examine clonality in 46 female patients along with assays for erythropoietin-independent erythroid colonies (EECs) and granulocyte PRV-1 mRNA levels to discriminate polycythemias and thrombocytoses.