author_facet Aichberger, Karl J.
Mayerhofer, Matthias
Krauth, Maria-Theresa
Vales, Anna
Derdak, Sophia
Pickl, Winfried F.
Sillaber, Christian
Valent, Peter
Aichberger, Karl J.
Mayerhofer, Matthias
Krauth, Maria-Theresa
Vales, Anna
Derdak, Sophia
Pickl, Winfried F.
Sillaber, Christian
Valent, Peter
author Aichberger, Karl J.
Mayerhofer, Matthias
Krauth, Maria-Theresa
Vales, Anna
Derdak, Sophia
Pickl, Winfried F.
Sillaber, Christian
Valent, Peter
spellingShingle Aichberger, Karl J.
Mayerhofer, Matthias
Krauth, Maria-Theresa
Vales, Anna
Derdak, Sophia
Pickl, Winfried F.
Sillaber, Christian
Valent, Peter
Blood
BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
Cell Biology
Hematology
Immunology
Biochemistry
author_sort aichberger, karl j.
spelling Aichberger, Karl J. Mayerhofer, Matthias Krauth, Maria-Theresa Vales, Anna Derdak, Sophia Pickl, Winfried F. Sillaber, Christian Valent, Peter 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v106.11.4835.4835 <jats:title>Abstract</jats:title> <jats:p>Basophil numbers are typically elevated in patients with chronic myeloid leukemia (CML) and characteristically increase during disease progression. As a consequence, blood histamine levels are highly upregulated in CML. We examined the biochemical basis of production of histamine in CML cells and analyzed the effects of the CML-related oncoprotein BCR/ABL on the generation of this mediator. Expression of histamine and of histidine decarboxylase (HDC), the major enzyme involved in histamine synthesis, were examined in primary CML cells obtained from patients with chronic phase (CP) CML or accelerated phase (AP) CML with basophilia, in the CML-derived cell lines K562 and KU812, and in Ba/F3 cells inducibly expressing BCR/ABL on exposure to doxycycline (TonB.210-X cells). In all patients with AP-CML and basophilia, high levels of HDC mRNA and of histamine were detected, whereas in CP-CML cells only expressed low amounts of HDC and of histamine. HDC mRNA and histamine were detectable in the basophil-committed CML cell line KU812, but not in K562 cells. Exposure of primary CML cells or KU812 cells to the BCR/ABL tyrosine kinase inhibitors imatinib (1 μM; Novartis Pharma AG) or AMN107 (100 nM; Novartis Pharma AG) decreased the levels of histamine and expression of HDC in BCR/ABL-transformed cells. Moreover, BCR/ABL was found to promote the expression of HDC mRNA and to increase the levels of histamine in TonB.210-X cells. The BCR/ABL-induced synthesis of histamine in these cells was blocked by the PI3-kinase inhibitor LY294002, whereas neither the MEK inhibitor PD98059, nor the mTOR inhibitor rapamycin affected histamine levels. In conclusion, our data show that the CML-specific oncoprotein BCR/ABL induces expression of HDC and synthesis of histamine in leukemic cells through a pathway involving the PI3-kinase.</jats:p> BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells. Blood
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title BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_unstemmed BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_full BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_fullStr BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_full_unstemmed BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_short BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_sort bcr/abl induces expression of histidine decarboxylase and synthesis of histamine in cml cells.
topic Cell Biology
Hematology
Immunology
Biochemistry
url http://dx.doi.org/10.1182/blood.v106.11.4835.4835
publishDate 2005
physical 4835-4835
description <jats:title>Abstract</jats:title> <jats:p>Basophil numbers are typically elevated in patients with chronic myeloid leukemia (CML) and characteristically increase during disease progression. As a consequence, blood histamine levels are highly upregulated in CML. We examined the biochemical basis of production of histamine in CML cells and analyzed the effects of the CML-related oncoprotein BCR/ABL on the generation of this mediator. Expression of histamine and of histidine decarboxylase (HDC), the major enzyme involved in histamine synthesis, were examined in primary CML cells obtained from patients with chronic phase (CP) CML or accelerated phase (AP) CML with basophilia, in the CML-derived cell lines K562 and KU812, and in Ba/F3 cells inducibly expressing BCR/ABL on exposure to doxycycline (TonB.210-X cells). In all patients with AP-CML and basophilia, high levels of HDC mRNA and of histamine were detected, whereas in CP-CML cells only expressed low amounts of HDC and of histamine. HDC mRNA and histamine were detectable in the basophil-committed CML cell line KU812, but not in K562 cells. Exposure of primary CML cells or KU812 cells to the BCR/ABL tyrosine kinase inhibitors imatinib (1 μM; Novartis Pharma AG) or AMN107 (100 nM; Novartis Pharma AG) decreased the levels of histamine and expression of HDC in BCR/ABL-transformed cells. Moreover, BCR/ABL was found to promote the expression of HDC mRNA and to increase the levels of histamine in TonB.210-X cells. The BCR/ABL-induced synthesis of histamine in these cells was blocked by the PI3-kinase inhibitor LY294002, whereas neither the MEK inhibitor PD98059, nor the mTOR inhibitor rapamycin affected histamine levels. In conclusion, our data show that the CML-specific oncoprotein BCR/ABL induces expression of HDC and synthesis of histamine in leukemic cells through a pathway involving the PI3-kinase.</jats:p>
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author Aichberger, Karl J., Mayerhofer, Matthias, Krauth, Maria-Theresa, Vales, Anna, Derdak, Sophia, Pickl, Winfried F., Sillaber, Christian, Valent, Peter
author_facet Aichberger, Karl J., Mayerhofer, Matthias, Krauth, Maria-Theresa, Vales, Anna, Derdak, Sophia, Pickl, Winfried F., Sillaber, Christian, Valent, Peter, Aichberger, Karl J., Mayerhofer, Matthias, Krauth, Maria-Theresa, Vales, Anna, Derdak, Sophia, Pickl, Winfried F., Sillaber, Christian, Valent, Peter
author_sort aichberger, karl j.
container_issue 11
container_start_page 4835
container_title Blood
container_volume 106
description <jats:title>Abstract</jats:title> <jats:p>Basophil numbers are typically elevated in patients with chronic myeloid leukemia (CML) and characteristically increase during disease progression. As a consequence, blood histamine levels are highly upregulated in CML. We examined the biochemical basis of production of histamine in CML cells and analyzed the effects of the CML-related oncoprotein BCR/ABL on the generation of this mediator. Expression of histamine and of histidine decarboxylase (HDC), the major enzyme involved in histamine synthesis, were examined in primary CML cells obtained from patients with chronic phase (CP) CML or accelerated phase (AP) CML with basophilia, in the CML-derived cell lines K562 and KU812, and in Ba/F3 cells inducibly expressing BCR/ABL on exposure to doxycycline (TonB.210-X cells). In all patients with AP-CML and basophilia, high levels of HDC mRNA and of histamine were detected, whereas in CP-CML cells only expressed low amounts of HDC and of histamine. HDC mRNA and histamine were detectable in the basophil-committed CML cell line KU812, but not in K562 cells. Exposure of primary CML cells or KU812 cells to the BCR/ABL tyrosine kinase inhibitors imatinib (1 μM; Novartis Pharma AG) or AMN107 (100 nM; Novartis Pharma AG) decreased the levels of histamine and expression of HDC in BCR/ABL-transformed cells. Moreover, BCR/ABL was found to promote the expression of HDC mRNA and to increase the levels of histamine in TonB.210-X cells. The BCR/ABL-induced synthesis of histamine in these cells was blocked by the PI3-kinase inhibitor LY294002, whereas neither the MEK inhibitor PD98059, nor the mTOR inhibitor rapamycin affected histamine levels. In conclusion, our data show that the CML-specific oncoprotein BCR/ABL induces expression of HDC and synthesis of histamine in leukemic cells through a pathway involving the PI3-kinase.</jats:p>
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imprint_str_mv American Society of Hematology, 2005
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spelling Aichberger, Karl J. Mayerhofer, Matthias Krauth, Maria-Theresa Vales, Anna Derdak, Sophia Pickl, Winfried F. Sillaber, Christian Valent, Peter 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v106.11.4835.4835 <jats:title>Abstract</jats:title> <jats:p>Basophil numbers are typically elevated in patients with chronic myeloid leukemia (CML) and characteristically increase during disease progression. As a consequence, blood histamine levels are highly upregulated in CML. We examined the biochemical basis of production of histamine in CML cells and analyzed the effects of the CML-related oncoprotein BCR/ABL on the generation of this mediator. Expression of histamine and of histidine decarboxylase (HDC), the major enzyme involved in histamine synthesis, were examined in primary CML cells obtained from patients with chronic phase (CP) CML or accelerated phase (AP) CML with basophilia, in the CML-derived cell lines K562 and KU812, and in Ba/F3 cells inducibly expressing BCR/ABL on exposure to doxycycline (TonB.210-X cells). In all patients with AP-CML and basophilia, high levels of HDC mRNA and of histamine were detected, whereas in CP-CML cells only expressed low amounts of HDC and of histamine. HDC mRNA and histamine were detectable in the basophil-committed CML cell line KU812, but not in K562 cells. Exposure of primary CML cells or KU812 cells to the BCR/ABL tyrosine kinase inhibitors imatinib (1 μM; Novartis Pharma AG) or AMN107 (100 nM; Novartis Pharma AG) decreased the levels of histamine and expression of HDC in BCR/ABL-transformed cells. Moreover, BCR/ABL was found to promote the expression of HDC mRNA and to increase the levels of histamine in TonB.210-X cells. The BCR/ABL-induced synthesis of histamine in these cells was blocked by the PI3-kinase inhibitor LY294002, whereas neither the MEK inhibitor PD98059, nor the mTOR inhibitor rapamycin affected histamine levels. In conclusion, our data show that the CML-specific oncoprotein BCR/ABL induces expression of HDC and synthesis of histamine in leukemic cells through a pathway involving the PI3-kinase.</jats:p> BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells. Blood
spellingShingle Aichberger, Karl J., Mayerhofer, Matthias, Krauth, Maria-Theresa, Vales, Anna, Derdak, Sophia, Pickl, Winfried F., Sillaber, Christian, Valent, Peter, Blood, BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells., Cell Biology, Hematology, Immunology, Biochemistry
title BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_full BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_fullStr BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_full_unstemmed BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_short BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
title_sort bcr/abl induces expression of histidine decarboxylase and synthesis of histamine in cml cells.
title_unstemmed BCR/ABL Induces Expression of Histidine Decarboxylase and Synthesis of Histamine in CML Cells.
topic Cell Biology, Hematology, Immunology, Biochemistry
url http://dx.doi.org/10.1182/blood.v106.11.4835.4835