scholarly journals Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1093-1101 ◽  
Author(s):  
N Sato ◽  
Y Takahashi ◽  
S Asano
Keyword(s):  
Alkaline Phosphatase ◽  
Retinoic Acid ◽  
Quantitative Polymerase Chain Reaction ◽  
Polymerase Chain Reaction Method ◽  
Granulocyte Colony Stimulating Factor ◽  
Chromosomal Structure ◽  
Polymerase Chain ◽  
Stimulating Factor ◽  
In Vitro Treatment

Abstract Alkaline phosphatase in neutrophils (NAP) is a product of the liver/bone/kidney-type alkaline phosphatase gene, the chromosomal structure of which has recently been analyzed. The gene has two alternative leader sequences resulting in the two types of mRNA (liver- type and bone-type mRNAs), which suggests that the expression of the gene is regulated by independent promoters. To determine the mechanism underlying NAP induction, it is essential to know which type of the mRNAs is dominant in neutrophils. We adopted quantitative polymerase chain reaction method to determine the relative amount of bone-type mRNA in neutrophils. The bone-type mRNA was found to be at least 5 times more than the liver-type mRNA. mRNA of NAP is known to be induced by in vitro treatment of the cells with granulocyte colony-stimulating factor (G-CSF), which is enhanced by a simultaneous addition of retinoic acid. In neutrophils treated with G-CSF, the bone-type mRNA was at least 6 times more than the liver-type mRNA. In neutrophils treated by both G-CSF and retinoic acid, the bone-type mRNA was at least 22 times more than the liver-type mRNA. The results show that the bone-type mRNA is predominantly transcribed in peripheral neutrophils and in neutrophils cultured in vitro.

scholarly journals Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1093-1101 ◽  
Author(s):  
N Sato ◽  
Y Takahashi ◽  
S Asano
Keyword(s):  
Alkaline Phosphatase ◽  
Retinoic Acid ◽  
Quantitative Polymerase Chain Reaction ◽  
Polymerase Chain Reaction Method ◽  
Granulocyte Colony Stimulating Factor ◽  
Chromosomal Structure ◽  
Polymerase Chain ◽  
Stimulating Factor ◽  
In Vitro Treatment

Alkaline phosphatase in neutrophils (NAP) is a product of the liver/bone/kidney-type alkaline phosphatase gene, the chromosomal structure of which has recently been analyzed. The gene has two alternative leader sequences resulting in the two types of mRNA (liver- type and bone-type mRNAs), which suggests that the expression of the gene is regulated by independent promoters. To determine the mechanism underlying NAP induction, it is essential to know which type of the mRNAs is dominant in neutrophils. We adopted quantitative polymerase chain reaction method to determine the relative amount of bone-type mRNA in neutrophils. The bone-type mRNA was found to be at least 5 times more than the liver-type mRNA. mRNA of NAP is known to be induced by in vitro treatment of the cells with granulocyte colony-stimulating factor (G-CSF), which is enhanced by a simultaneous addition of retinoic acid. In neutrophils treated with G-CSF, the bone-type mRNA was at least 6 times more than the liver-type mRNA. In neutrophils treated by both G-CSF and retinoic acid, the bone-type mRNA was at least 22 times more than the liver-type mRNA. The results show that the bone-type mRNA is predominantly transcribed in peripheral neutrophils and in neutrophils cultured in vitro.

scholarly journals Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1909-1921 ◽  
Author(s):  
M Gianni ◽  
M Terao ◽  
S Zanotta ◽  
T Barbui ◽  
A Rambaldi ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Nb4 Cells ◽  
Leukocyte Alkaline Phosphatase ◽  
Stimulating Factor

Abstract In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes. In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML), in the stable phase of the disease, a weaker interaction between ATRA and G- CSF was documented. The cross-talk between the cytokine and the retinoid was studied in detail in NB4, an immortalized APL leukemia cell line, retaining the 15′17 chromosomal translocation involving the retinoic acid receptor type alpha. The treatment of NB4 cells with G- CSF alone or ATRA alone leads to no increase and to minor induction in LAP activity, respectively. If the cells are treated with the two compounds simultaneously, a dramatic elevation of LAP is observed after 4 days. The synergism between G-CSF and ATRA is evident at concentrations of the retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine between 1 and 10 ng/mL. The simultaneous presence of the two compounds is necessary to obtain maximal increase of LAP activity and the effect is cell density-dependent. Synergism is specific for G-CSF, and it is not observed with other cytokines and functional inducers of the granulocyte. The augmentation of LAP activity is the consequence of an increased transcriptional rate of the liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by Northern blotting and nuclear run-on analysis using specific cDNA probes. Only one of the two possible alternatively spliced forms of L/B/K-type alkaline phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and ATRA. This mRNA form, which is the one observed in normal polymorphonuclear leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G- CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor effects on the expression of these mRNAs.

Granulocyte Colony-Stimulating Factor–Producing Undifferentiated Sarcoma Occurring in Previously Fractured Femur

2003 ◽  
Vol 127 (4) ◽  
pp. e186-e189
Author(s):  
Takashi Marui ◽  
Tetsuji Yamamoto ◽  
Toshihiro Akisue ◽  
Toshiaki Hitora ◽  
Shinichi Yoshiya ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Culture Medium ◽  
Soft Tissue Tumor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Undifferentiated Sarcoma ◽  
Genomic Study ◽  
Polymerase Chain ◽  
Stimulating Factor

Abstract We examined the case of a 52-year-old man presenting with a sarcoma accompanied by severe leukocytosis, which developed many years after a femoral fracture. Histologic, histochemical, immunohistochemical, and ultrastructural analysis of the tumor revealed that the sarcoma could not be classified by any of the bone or soft tissue tumor classifications currently in use. The tumor cells were isolated from surgical specimens and subcultured in vitro. The concentration of granulocyte colony-stimulating factor in the culture medium was constantly elevated to considerably high levels during 20 cell passages. A genomic study using reverse transcription–polymerase chain reaction showed that the cells retained messenger RNA expression of granulocyte colony-stimulating factor. The aberrant overexpression of granulocyte colony-stimulating factor clearly represented a paraneoplastic phenomenon of the neoplastic cells.

scholarly journals Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1909-1921 ◽  
Author(s):  
M Gianni ◽  
M Terao ◽  
S Zanotta ◽  
T Barbui ◽  
A Rambaldi ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Nb4 Cells ◽  
Leukocyte Alkaline Phosphatase ◽  
Stimulating Factor

In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes. In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML), in the stable phase of the disease, a weaker interaction between ATRA and G- CSF was documented. The cross-talk between the cytokine and the retinoid was studied in detail in NB4, an immortalized APL leukemia cell line, retaining the 15′17 chromosomal translocation involving the retinoic acid receptor type alpha. The treatment of NB4 cells with G- CSF alone or ATRA alone leads to no increase and to minor induction in LAP activity, respectively. If the cells are treated with the two compounds simultaneously, a dramatic elevation of LAP is observed after 4 days. The synergism between G-CSF and ATRA is evident at concentrations of the retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine between 1 and 10 ng/mL. The simultaneous presence of the two compounds is necessary to obtain maximal increase of LAP activity and the effect is cell density-dependent. Synergism is specific for G-CSF, and it is not observed with other cytokines and functional inducers of the granulocyte. The augmentation of LAP activity is the consequence of an increased transcriptional rate of the liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by Northern blotting and nuclear run-on analysis using specific cDNA probes. Only one of the two possible alternatively spliced forms of L/B/K-type alkaline phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and ATRA. This mRNA form, which is the one observed in normal polymorphonuclear leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G- CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor effects on the expression of these mRNAs.

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