scholarly journals Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts

2001 ◽  
Vol 67 (4) ◽  
pp. 267-278 ◽  
Author(s):  
Brynjar Foss ◽  
Elling Ulvestad ◽  
Øystein Bruserud
Keyword(s):  
Growth Factor ◽  
Acute Myelogenous Leukemia ◽  
Receptor Expression ◽  
Myelogenous Leukemia ◽  
Platelet Derived Growth Factor ◽  
Pdgf Receptor ◽  
Acute Myelogenous ◽  
Pdgf Isoforms

scholarly journals Fusion of the Platelet-Derived Growth Factor Receptor β to a Novel Gene CEV14 in Acute Myelogenous Leukemia After Clonal Evolution

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4271-4277 ◽  
Author(s):  
Akihiro Abe ◽  
Nobuhiko Emi ◽  
Mitsune Tanimoto ◽  
Hiroshi Terasaki ◽  
Toru Marunouchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Acute Myelogenous Leukemia ◽  
Fusion Gene ◽  
Growth Factor Receptor ◽  
Initial Diagnosis ◽  
Myelogenous Leukemia ◽  
Platelet Derived Growth Factor ◽  
Novel Gene ◽  
Wide Range ◽  
Acute Myelogenous

Abstract Chromosomal translocations involving band 5q31-35 occur in several hematologic disorders. A clone with a t(5; 14)(q33; q32) translocation appeared at the relapse phase in a patient with acute myelogenous leukemia who exhibited a sole chromosomal translocation, t(7; 11), at initial diagnosis. After the appearance of this clone, the leukemia progressed with marked eosinophilia, and combination chemotherapy was ineffective. Southern blot analysis showed a rearrangement of the platelet-derived growth factor receptor β (PDGFRβ) gene at 5q33 which was not observed at initial diagnosis. This translocation resulted in a chimeric transcript fusing the PDGFRβ gene on 5q33 with a novel gene, CEV14, located at 14q32. Expression of the 5′ region of the PDGFRβ cDNA, upstream of the breakpoint, was not detected. However, the 3′ region of PDGFRβ, which was transcribed as part of the CEV14-PDGFRβ fusion gene, was detected. A partial cDNA for a novel gene, CEV14, includes a leucine zipper motif and putative thyroid hormone receptor interacting domain and is expressed in a wide range of tissues. The expression of a CEV14-PDGFRβ fusion gene in association with aggressive leukemia progression suggests that this protein has oncogenic potential.

Calcium and growth responses of hyperresponsive airway smooth muscle to different isoforms of platelet-derived growth factor (PDGF)

2000 ◽  
Vol 78 (11) ◽  
pp. 867-873 ◽  
Author(s):  
Mary E Zacour ◽  
Barbara Tolloczko ◽  
James G Martin
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Receptor Expression ◽  
Platelet Derived Growth Factor ◽  
Pdgf Receptor ◽  
Growth Responses ◽  
Mitogenic Response ◽  
Pdgf Isoforms

Airway smooth muscle (ASM) mass is likely to be an important determinant of airway responsiveness. Highly inbred Fisher rats model innate hyperresponsiveness, and also have more ASM in vivo than control Lewis rats. Platelet derived growth factor (PDGF) is an important endogenous growth factor for ASM, and partially purified PDGF-AB causes enhanced growth of Fisher rat ASM cells, compared to Lewis cells. The aim of the present study was to determine the mitogenic effects of all three recombinant PDGF isoforms on ASM cells, and investigate the mechanisms of enhanced Fisher ASM growth responses. The potential mechanisms assessed include PDGF receptor expression and activation (tyrosine phoshorylation), and intracellular calcium (Ca2+) responses to PDGF isoforms. Fisher ASM cells had a greater mitogenic response to PDGF-AB and -AA, and a greater Ca2+ response to -BB than Lewis ASM cells. A Ca2+ response was not necessary for a mitogenic response, and the effects of PDGF isoforms on Ca2+ were not associated with their effects on growth. Therefore, we suggest that enhanced Fisher mitogenic response to PDGF-AA and -AB is not mediated by differences in Ca2+ signalling. Western analysis of the PDGF receptor indicated a similar expression of β-PDGF receptor in ASM cells from the two rat strains, but a greater expression of α-PDGF receptor in Fisher cells; however, phosphorylation of the PDGF receptor following growth stimulation did not differ between strains. This suggests a role for post-receptor signals, in addition to enhanced receptor expression, in the enhanced growth response of Fisher ASM cells to PDGF-AA and -AB.Key words: PDGF receptors, tyrosine phosphorylation, intracellular calcium, proliferation, airway smooth muscle cells.

scholarly journals Fusion of the Platelet-Derived Growth Factor Receptor β to a Novel Gene CEV14 in Acute Myelogenous Leukemia After Clonal Evolution

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4271-4277 ◽  
Author(s):  
Akihiro Abe ◽  
Nobuhiko Emi ◽  
Mitsune Tanimoto ◽  
Hiroshi Terasaki ◽  
Toru Marunouchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Acute Myelogenous Leukemia ◽  
Fusion Gene ◽  
Growth Factor Receptor ◽  
Initial Diagnosis ◽  
Myelogenous Leukemia ◽  
Platelet Derived Growth Factor ◽  
Novel Gene ◽  
Wide Range ◽  
Acute Myelogenous

Chromosomal translocations involving band 5q31-35 occur in several hematologic disorders. A clone with a t(5; 14)(q33; q32) translocation appeared at the relapse phase in a patient with acute myelogenous leukemia who exhibited a sole chromosomal translocation, t(7; 11), at initial diagnosis. After the appearance of this clone, the leukemia progressed with marked eosinophilia, and combination chemotherapy was ineffective. Southern blot analysis showed a rearrangement of the platelet-derived growth factor receptor β (PDGFRβ) gene at 5q33 which was not observed at initial diagnosis. This translocation resulted in a chimeric transcript fusing the PDGFRβ gene on 5q33 with a novel gene, CEV14, located at 14q32. Expression of the 5′ region of the PDGFRβ cDNA, upstream of the breakpoint, was not detected. However, the 3′ region of PDGFRβ, which was transcribed as part of the CEV14-PDGFRβ fusion gene, was detected. A partial cDNA for a novel gene, CEV14, includes a leucine zipper motif and putative thyroid hormone receptor interacting domain and is expressed in a wide range of tissues. The expression of a CEV14-PDGFRβ fusion gene in association with aggressive leukemia progression suggests that this protein has oncogenic potential.

Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex

1990 ◽  
Vol 10 (5) ◽  
pp. 2359-2366
Author(s):  
D K Morrison ◽  
D R Kaplan ◽  
S G Rhee ◽  
L T Williams
Keyword(s):  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Serine Phosphorylation ◽  
Platelet Derived Growth Factor ◽  
Pdgf Receptor ◽  
Wild Type ◽  
Receptor Proteins ◽  
Signaling Complex

We investigated the interaction of phospholipase C-gamma (PLC-gamma) with wild-type and mutant forms of the platelet-derived growth factor (PDGF) beta-receptor both in vivo and in vitro. After PDGF treatment of CHO cell lines expressing wild-type or either of two mutant (delta Ki and Y825F) PDGF receptors, PLC-gamma became tyrosine phosphorylated and associated with the receptor proteins. The receptor association and tyrosine phosphorylation of PLC-gamma correlated with the ability of these receptors to mediate ligand-induced phosphatidylinositol turnover. However, both the delta Ki and Y825F mutant receptors were deficient in transmitting mitogenic signals, suggesting that the PDGF-induced tyrosine phosphorylation and receptor association of PLC-gamma are not sufficient to account for the growth-stimulatory activity of PDGF. Wild-type and delta Ki mutant PDGF receptor proteins expressed with recombinant baculovirus vectors also associated in vitro with mammalian PLC-gamma. However, baculovirus-expressed c-fms, v-fms, c-src, and Raf-1 proteins failed to associate with PLC-gamma under similar conditions. Phosphatase treatment of the baculovirus-expressed PDGF receptor greatly decreased its association with PLC-gamma. This requirement for receptor phosphorylation was also observed in vivo, where PLC-gamma could not associate with a mutant PDGF receptor (K602A) defective in autophosphorylation. PLC-gamma also coimmunoprecipitated with two other putative receptor substrates, the serine-threonine kinase Raf-1 and the 85-kilodalton phosphatidylinositol-3' kinase, presumably through its association with the ligand-activated receptor. Furthermore, baculovirus-expressed Raf-1 phosphorylated purified PLC-gamma in vitro at sites which showed increased serine phosphorylation in vivo in response to PDGF. These results suggest that PDGF directly influences PLC activity by inducing the association of PLC-gamma with a receptor signaling complex, resulting in increased tyrosine and serine phosphorylation of PLC-gamma.

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