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Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | Blood, 107, 2006, 4, S. 1570-1581 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Ge, Yubin Dombkowski, Alan A. LaFiura, Katherine M. Tatman, Dana Yedidi, Ravikiran S. Stout, Mark L. Buck, Steven A. Massey, Gita Becton, David L. Weinstein, Howard J. Ravindranath, Yaddanapudi Matherly, Larry H. Taub, Jeffrey W. Ge, Yubin Dombkowski, Alan A. LaFiura, Katherine M. Tatman, Dana Yedidi, Ravikiran S. Stout, Mark L. Buck, Steven A. Massey, Gita Becton, David L. Weinstein, Howard J. Ravindranath, Yaddanapudi Matherly, Larry H. Taub, Jeffrey W. |
|---|---|
| author |
Ge, Yubin Dombkowski, Alan A. LaFiura, Katherine M. Tatman, Dana Yedidi, Ravikiran S. Stout, Mark L. Buck, Steven A. Massey, Gita Becton, David L. Weinstein, Howard J. Ravindranath, Yaddanapudi Matherly, Larry H. Taub, Jeffrey W. |
| spellingShingle |
Ge, Yubin Dombkowski, Alan A. LaFiura, Katherine M. Tatman, Dana Yedidi, Ravikiran S. Stout, Mark L. Buck, Steven A. Massey, Gita Becton, David L. Weinstein, Howard J. Ravindranath, Yaddanapudi Matherly, Larry H. Taub, Jeffrey W. Blood Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia Cell Biology Hematology Immunology Biochemistry |
| author_sort |
ge, yubin |
| spelling |
Ge, Yubin Dombkowski, Alan A. LaFiura, Katherine M. Tatman, Dana Yedidi, Ravikiran S. Stout, Mark L. Buck, Steven A. Massey, Gita Becton, David L. Weinstein, Howard J. Ravindranath, Yaddanapudi Matherly, Larry H. Taub, Jeffrey W. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-06-2219 <jats:p>Children with Down syndrome (DS) with acute megakaryocytic leukemia (AMkL) have very high survival rates compared with non-DS AMkL patients. Somatic mutations identified in the X-linked transcription factor gene, GATA1, in essentially all DS AMkL cases result in the synthesis of a shorter (40 kDa) protein (GATA1s) with altered transactivation activity and may lead to altered expression of GATA1 target genes. Using the Affymetrix U133A microarray chip, we identified 551 differentially expressed genes between DS and non-DS AMkL samples. Transcripts for the bone marrow stromal-cell antigen 2 (BST2) gene, encoding a transmembrane glycoprotein potentially involved in interactions between leukemia cells and bone marrow stromal cells, were 7.3-fold higher (validated by real-time polymerase chain reaction) in the non-DS compared with the DS group. Additional studies confirmed GATA1 protein binding and transactivation of the BST2 promoter; however, stimulation of BST2 promoter activity by GATA1s was substantially reduced compared with the full-length GATA1. CMK sublines, transfected with the BST2 cDNA and incubated with HS-5 bone marrow stromal cells, exhibited up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected cells. Our results demonstrate that genes that account for differences in survival between DS and non-DS AMkL cases may be identified by microarray analysis and that differential gene expression may reflect relative transactivation capacities of the GATA1s and full-length GATA1 proteins.</jats:p> Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia Blood |
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| title |
Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_unstemmed |
Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_full |
Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_fullStr |
Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_full_unstemmed |
Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_short |
Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_sort |
differential gene expression, gata1 target genes, and the chemotherapy sensitivity of down syndrome megakaryocytic leukemia |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2005-06-2219 |
| publishDate |
2006 |
| physical |
1570-1581 |
| description |
<jats:p>Children with Down syndrome (DS) with acute megakaryocytic leukemia (AMkL) have very high survival rates compared with non-DS AMkL patients. Somatic mutations identified in the X-linked transcription factor gene, GATA1, in essentially all DS AMkL cases result in the synthesis of a shorter (40 kDa) protein (GATA1s) with altered transactivation activity and may lead to altered expression of GATA1 target genes. Using the Affymetrix U133A microarray chip, we identified 551 differentially expressed genes between DS and non-DS AMkL samples. Transcripts for the bone marrow stromal-cell antigen 2 (BST2) gene, encoding a transmembrane glycoprotein potentially involved in interactions between leukemia cells and bone marrow stromal cells, were 7.3-fold higher (validated by real-time polymerase chain reaction) in the non-DS compared with the DS group. Additional studies confirmed GATA1 protein binding and transactivation of the BST2 promoter; however, stimulation of BST2 promoter activity by GATA1s was substantially reduced compared with the full-length GATA1. CMK sublines, transfected with the BST2 cDNA and incubated with HS-5 bone marrow stromal cells, exhibited up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected cells. Our results demonstrate that genes that account for differences in survival between DS and non-DS AMkL cases may be identified by microarray analysis and that differential gene expression may reflect relative transactivation capacities of the GATA1s and full-length GATA1 proteins.</jats:p> |
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| author | Ge, Yubin, Dombkowski, Alan A., LaFiura, Katherine M., Tatman, Dana, Yedidi, Ravikiran S., Stout, Mark L., Buck, Steven A., Massey, Gita, Becton, David L., Weinstein, Howard J., Ravindranath, Yaddanapudi, Matherly, Larry H., Taub, Jeffrey W. |
| author_facet | Ge, Yubin, Dombkowski, Alan A., LaFiura, Katherine M., Tatman, Dana, Yedidi, Ravikiran S., Stout, Mark L., Buck, Steven A., Massey, Gita, Becton, David L., Weinstein, Howard J., Ravindranath, Yaddanapudi, Matherly, Larry H., Taub, Jeffrey W., Ge, Yubin, Dombkowski, Alan A., LaFiura, Katherine M., Tatman, Dana, Yedidi, Ravikiran S., Stout, Mark L., Buck, Steven A., Massey, Gita, Becton, David L., Weinstein, Howard J., Ravindranath, Yaddanapudi, Matherly, Larry H., Taub, Jeffrey W. |
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| description | <jats:p>Children with Down syndrome (DS) with acute megakaryocytic leukemia (AMkL) have very high survival rates compared with non-DS AMkL patients. Somatic mutations identified in the X-linked transcription factor gene, GATA1, in essentially all DS AMkL cases result in the synthesis of a shorter (40 kDa) protein (GATA1s) with altered transactivation activity and may lead to altered expression of GATA1 target genes. Using the Affymetrix U133A microarray chip, we identified 551 differentially expressed genes between DS and non-DS AMkL samples. Transcripts for the bone marrow stromal-cell antigen 2 (BST2) gene, encoding a transmembrane glycoprotein potentially involved in interactions between leukemia cells and bone marrow stromal cells, were 7.3-fold higher (validated by real-time polymerase chain reaction) in the non-DS compared with the DS group. Additional studies confirmed GATA1 protein binding and transactivation of the BST2 promoter; however, stimulation of BST2 promoter activity by GATA1s was substantially reduced compared with the full-length GATA1. CMK sublines, transfected with the BST2 cDNA and incubated with HS-5 bone marrow stromal cells, exhibited up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected cells. Our results demonstrate that genes that account for differences in survival between DS and non-DS AMkL cases may be identified by microarray analysis and that differential gene expression may reflect relative transactivation capacities of the GATA1s and full-length GATA1 proteins.</jats:p> |
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| imprint | American Society of Hematology, 2006 |
| imprint_str_mv | American Society of Hematology, 2006 |
| institution | DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3 |
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| spelling | Ge, Yubin Dombkowski, Alan A. LaFiura, Katherine M. Tatman, Dana Yedidi, Ravikiran S. Stout, Mark L. Buck, Steven A. Massey, Gita Becton, David L. Weinstein, Howard J. Ravindranath, Yaddanapudi Matherly, Larry H. Taub, Jeffrey W. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-06-2219 <jats:p>Children with Down syndrome (DS) with acute megakaryocytic leukemia (AMkL) have very high survival rates compared with non-DS AMkL patients. Somatic mutations identified in the X-linked transcription factor gene, GATA1, in essentially all DS AMkL cases result in the synthesis of a shorter (40 kDa) protein (GATA1s) with altered transactivation activity and may lead to altered expression of GATA1 target genes. Using the Affymetrix U133A microarray chip, we identified 551 differentially expressed genes between DS and non-DS AMkL samples. Transcripts for the bone marrow stromal-cell antigen 2 (BST2) gene, encoding a transmembrane glycoprotein potentially involved in interactions between leukemia cells and bone marrow stromal cells, were 7.3-fold higher (validated by real-time polymerase chain reaction) in the non-DS compared with the DS group. Additional studies confirmed GATA1 protein binding and transactivation of the BST2 promoter; however, stimulation of BST2 promoter activity by GATA1s was substantially reduced compared with the full-length GATA1. CMK sublines, transfected with the BST2 cDNA and incubated with HS-5 bone marrow stromal cells, exhibited up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected cells. Our results demonstrate that genes that account for differences in survival between DS and non-DS AMkL cases may be identified by microarray analysis and that differential gene expression may reflect relative transactivation capacities of the GATA1s and full-length GATA1 proteins.</jats:p> Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia Blood |
| spellingShingle | Ge, Yubin, Dombkowski, Alan A., LaFiura, Katherine M., Tatman, Dana, Yedidi, Ravikiran S., Stout, Mark L., Buck, Steven A., Massey, Gita, Becton, David L., Weinstein, Howard J., Ravindranath, Yaddanapudi, Matherly, Larry H., Taub, Jeffrey W., Blood, Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_full | Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_fullStr | Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_full_unstemmed | Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_short | Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| title_sort | differential gene expression, gata1 target genes, and the chemotherapy sensitivity of down syndrome megakaryocytic leukemia |
| title_unstemmed | Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2005-06-2219 |