These results indicate an important role for SHP-1 in the regulation of normal human erythroid progenitors and suggest that defective expression of the protein may contribute to the pathogenesis of polycythemia vera.
These results indicate an important role for SHP-1 in the regulation of normal human erythroid progenitors and suggest that defective expression of the protein may contribute to the pathogenesis of polycythemia vera.
Following cDNA subtraction using mRNAs isolated from PV and normal CD34+/CD33- bone-marrow cells, expression of the tumour suppressor H19 was found to be low or absent in the PV sample.
We isolated a novel gene, subsequently named PRV-1, which is highly expressed in granulocytes from patients with PV (n = 19), but not detectable in normal control granulocytes (n = 21).
Taken together, these observations demonstrate that H19 and IGF2 are specifically expressed during haematopoiesis and that low levels of H19 expression are associated with PV and may contribute to the pathology of the disease.
Following cDNA subtraction using mRNAs isolated from PV and normal CD34+/CD33- bone-marrow cells, expression of the tumour suppressor H19 was found to be low or absent in the PV sample.
A number of cellular abnormalities associated with PV, including the hyperresponsiveness of PV progenitors to many cytokines as well as decreased expression of the thrombopoietin receptor on platelets and increased expression of Bcl-xL, suggest that the PV defect alters a number of cellular functions and is not restricted to cytokine receptor signal transduction.
A number of cellular abnormalities associated with PV, including the hyperresponsiveness of PV progenitors to many cytokines as well as decreased expression of the thrombopoietin receptor on platelets and increased expression of Bcl-xL, suggest that the PV defect alters a number of cellular functions and is not restricted to cytokine receptor signal transduction.
A number of cellular abnormalities associated with PV, including the hyperresponsiveness of PV progenitors to many cytokines as well as decreased expression of the thrombopoietin receptor on platelets and increased expression of Bcl-xL, suggest that the PV defect alters a number of cellular functions and is not restricted to cytokine receptor signal transduction.
Recently, enhanced tyrosine phosphorylation of the insulin-like growth factor-I receptor (IGF-IR) has been shown in PV bone marrow progenitors and peripheral blood mononuclear cells (PBMNC), and elevated levels of IGF binding protein-1 (IGFBP-1) in the serum of PV patients have been reported.
A further two patients with myelofibrosis secondary to polycythaemia vera and essential thrombocythaemia with reciprocal 13q translocations were studied in an attempt to further define the CDR.
A further two patients with myelofibrosis secondary to polycythaemia vera and essential thrombocythaemia with reciprocal 13q translocations were studied in an attempt to further define the CDR.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
We conclude that there is no direct impairment of IGF-IR structure or function, but an altered IGFBP profile in a significant portion of PV patients which might contribute to the pathogenesis of PV in these patients.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
Sequencing revealed no mutations of INK4a or ARF in 10 patients with PV. p16(INK4a) is an important negative cell-cycle regulator, but in contrast with a wide range of malignancies where inactivation of the INK4a gene is one of the most common carcinogenetic events, in PV p16( INK4a) expression was dramatically increased without a significant change in ECFC cell cycle compared with normal ECFCs.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.