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Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia

Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia
Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia
The functional consequences of a high-hyperdiploid karyotype, found in up to one-third of cases of acute lymphoblastic leukemia (ALL), are unknown. Using the technique of comparative expressed sequence hybridization (CESH), we sought to address the question of whether increased chromosome copies in hyperdiploid ALL lead to increased gene expression. Relative expression of hyperdiploid ALL blasts versus peripheral blood mononuclear cells was analyzed in 18 patients. Common regions of overexpression corresponding to the presence of tri-/tetrasomies included: Xp22.1-22.2, 4q28, 6q14-15, 6q24, 10p13, 14q23-24, 17q21, 18q12, and 21q21, identified in 28-89% of cases. However, increased expression without underlying trisomy occurred at 3p21.3, 7q11.2, 8p21, and 8q24.1 in 39-90% of cases. High expression at 7q11.2, the most consistent change detected, was confirmed by quantitative PCR. Poor correlation between the presence of tri-/tetrasomy and overexpression was observed for chromosomes 14 and 17. Two cases were reanalyzed versus (i) B cells, (ii) transformed B cells, and (iii) CD34+19+ cells (the putative counterpart of the leukemic cell). A reduction in the number of relatively overexpressed regions was observed with CD34+19+ cells. In particular, the peak at 7q11.2 disappeared, suggesting up-regulation of genes from this region in the early ontology of normal B-cell development. In conclusion, we have shown that tri-/tetrasomies in hyperdiploid ALL lead to an increase in the expression of associated sequences. The choice of a biologically relevant reference is crucial for data interpretation.
1045-2257
191-202
Gruszka-Westwood, Alicja M.
9c9b1f2b-970f-494a-b3ec-a6d84566328c
Horsley, Sharon W.
1b7de655-100e-458c-9880-80fc7443fab6
Martinez-Ramirez, Angel
195279f7-52ac-4ea0-8772-2e0f78552085
Harrison, Christine J.
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Kempski, Helena
a2db8f50-62b6-4baf-92a8-767f40a2563a
Moorman, Anthony V.
e4ced178-ee03-47ef-bc5e-25d8453951d5
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Griffiths, Michael
77bbc130-74ba-4cee-a1a6-c7dcefbf0900
Greaves, Mel F.
87f0d186-56f1-48cf-9ef3-e3dd1136b2f3
Kearney, Lyndal
ad57b9c8-b5e2-4a77-9a11-8d1e3827e298
Gruszka-Westwood, Alicja M.
9c9b1f2b-970f-494a-b3ec-a6d84566328c
Horsley, Sharon W.
1b7de655-100e-458c-9880-80fc7443fab6
Martinez-Ramirez, Angel
195279f7-52ac-4ea0-8772-2e0f78552085
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Kempski, Helena
a2db8f50-62b6-4baf-92a8-767f40a2563a
Moorman, Anthony V.
e4ced178-ee03-47ef-bc5e-25d8453951d5
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Griffiths, Michael
77bbc130-74ba-4cee-a1a6-c7dcefbf0900
Greaves, Mel F.
87f0d186-56f1-48cf-9ef3-e3dd1136b2f3
Kearney, Lyndal
ad57b9c8-b5e2-4a77-9a11-8d1e3827e298

Gruszka-Westwood, Alicja M., Horsley, Sharon W., Martinez-Ramirez, Angel, Harrison, Christine J., Kempski, Helena, Moorman, Anthony V., Ross, Fiona M., Griffiths, Michael, Greaves, Mel F. and Kearney, Lyndal (2004) Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia. Genes, Chromosomes and Cancer, 41 (3), 191-202. (doi:10.1002/gcc.20085).

Record type: Article

Abstract

The functional consequences of a high-hyperdiploid karyotype, found in up to one-third of cases of acute lymphoblastic leukemia (ALL), are unknown. Using the technique of comparative expressed sequence hybridization (CESH), we sought to address the question of whether increased chromosome copies in hyperdiploid ALL lead to increased gene expression. Relative expression of hyperdiploid ALL blasts versus peripheral blood mononuclear cells was analyzed in 18 patients. Common regions of overexpression corresponding to the presence of tri-/tetrasomies included: Xp22.1-22.2, 4q28, 6q14-15, 6q24, 10p13, 14q23-24, 17q21, 18q12, and 21q21, identified in 28-89% of cases. However, increased expression without underlying trisomy occurred at 3p21.3, 7q11.2, 8p21, and 8q24.1 in 39-90% of cases. High expression at 7q11.2, the most consistent change detected, was confirmed by quantitative PCR. Poor correlation between the presence of tri-/tetrasomy and overexpression was observed for chromosomes 14 and 17. Two cases were reanalyzed versus (i) B cells, (ii) transformed B cells, and (iii) CD34+19+ cells (the putative counterpart of the leukemic cell). A reduction in the number of relatively overexpressed regions was observed with CD34+19+ cells. In particular, the peak at 7q11.2 disappeared, suggesting up-regulation of genes from this region in the early ontology of normal B-cell development. In conclusion, we have shown that tri-/tetrasomies in hyperdiploid ALL lead to an increase in the expression of associated sequences. The choice of a biologically relevant reference is crucial for data interpretation.

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Published date: 2004

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Local EPrints ID: 26332
URI: http://eprints.soton.ac.uk/id/eprint/26332
ISSN: 1045-2257
PURE UUID: b1326ccb-323b-4bd2-a0cc-cc1a778226ff

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Date deposited: 21 Apr 2006
Last modified: 15 Mar 2024 07:09

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Contributors

Author: Alicja M. Gruszka-Westwood
Author: Sharon W. Horsley
Author: Angel Martinez-Ramirez
Author: Christine J. Harrison
Author: Helena Kempski
Author: Anthony V. Moorman
Author: Fiona M. Ross
Author: Michael Griffiths
Author: Mel F. Greaves
Author: Lyndal Kearney

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