Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular etiology of Polycythemia vera (PV) is still undetermined. 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. To identify further alterations of circulating IGFBPs, the IGFBP profile in the serum of 12 PV patients was compared with age- and sex-matched controls by Western ligand blot (WLB), two-dimensional WLB, IGFBP-3 immunoblot and specific RIA for IGFBP-1, -2, -3 and IGFBP-4. To elucidate a role for the IGF-IR in the pathogenesis of PV, basal and IGF-I stimulated tyrosine phosphorylation of the IGF-IR beta-subunit in PBMNC of PV patients or controls was determined by WLB. Furthermore, exons 2, 3 and 15-21 of the IGF-IR were screened for mutations by PCR-single strand conformation polymorphism analysis (PCR-SSCP). We found alterations of the IGFBP profile in the serum of eight out of 12 examined patients including elevated levels of IGFBP-1, -2 and -4, decreased levels of IGFBP-3 and an increase in IGFBP-3 fragment. However, no differences in tyrosine phosphorylation of the IGF-IR in PV patients, neither basal nor IGF-I induced, were detected. Furthermore, no mutations within the screened exons of the IGF-IR could be identified by PCR-SSCP. 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.
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PMID:Alterations of the insulin-like growth factor system in patients with polycythemia vera. 1147 52

The insulin-like growth factor (IGF) system regulates proliferation and differentiation of hematopoietic cells. IGFs exert their effects through specific receptors on growing and differentiating blood cells as they emerge from their small pool of ancestral stem cells. The IGF system is complex as both stimulating and inhibiting effects occur by interaction of IGFs and IGF-binding proteins (IGFBPs). IGFs stimulate erythrocytes and lymphocytes but also promote leukemic hematopoietic cell proliferation. IGF-I appears to be correlated with hemoglobin levels in anemia and could also be of benefit for patients with bone marrow aplasia after transplantation. Hypersensitivity to IGF-I has been implicated as an underlying cause of polycythemia vera. Loss of imprinting of IGF-II is found in acute myeloid leukemia and myelodysplastic syndrome. Apoptosis of hematopoietic cells is significantly reduced by IGF-I involving an intriguing signal transduction pathway. IGFs could therefore, although not classical hematopoietic growth factors, be of benefit for patients with diverse hematopoietic disorders.
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PMID:The insulin-like growth factor system in hematopoietic cells. 1200 50

The GH-IGF axis has been recently suggested to modulate blood rheology in trained athletes, via GH effects on body water status and a possible action of IGF-I on erythrocyte deformability and aggregability. Another potential candidate for such a rheologic effect of the GH-IGF axis is insulin-like growth factor binding protein-1 (IGF-BP1) which is increased in trained people and correlated to fitness: IGF-BP1 is elevated in patients with polycythemia vera and stimulates erythroid burst formation in vitro. We investigated the statistical relationships between IGF-BP1 and blood rheology in athletes. 21 soccer players, age 24.5+/-1.13 yr; body mass index 23.7+/-0.38 kg/m(2); VO2max 44.8+/-7 ml.min(-1).kg(-1)). The major statistical determinant of IGFBP1 (measured at rest after overnight fast) was age (r=0.752, p=0.00013) which was not correlated with rheological parameters. IGF BP1 was negatively correlated with blood viscosity eta (high shear rate r=-0.516, p=0.024) and positively correlated with the percentage of extracellular water in total body water (ECW/TBW) (r=0.488, p=0.039). The previously reported correlations between IGF-I and both eta (r=0.637, p=0.003) and red cell rigidity "Tk" (r=0.696, p=0.0137) were observed, but IGF-I and IGF-BP1 were not correlated to each other (r=-0.176 ns) and their correlations with eta and Tk appeared to be independent when studied by multivariate analysis. Consistent with these correlations, subjects in the upper tertile of IGF-BP1 (>23.4 ng/ml) compared to those in the lower (<7.5 ng/ml) had a higher percentage of ECW/TBW (40.8+/-0.4 vs 38+/-0.8%, p=0.033), a lower eta (2.7+/-0.05 vs 2.97+/-0.06 mPa.s, p=0.016), and a lower Tk (0.54+/-0.05 vs 0.63+/-0.01, p=0.027). Thus, beside GH and IGF-I, IGF-BP1, which is reported to act on erythroid progenitors, exhibits statistical relationships with blood fluidity and erythrocyte flexibility that may suggest a physiological role in improving blood rheology.
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PMID:Insulin-like growth factor-binding protein 1 and blood rheology in athletes. 1208 53