Abstract
The molecular pathogenesis of B cell chronic lymphocytic leukemia (B-CLL), the most common form of leukemia, remains unknown. We have used the mRNA differential display technique to analyze genes that may be involved in the development/progression of B-CLL. We have identified the tumor suppressor retinoic acid receptor responder 3 (RARRES3) as a B-CLL-related gene. RARRES3 maps to chromosome band 11q23, a region frequently deleted in lymphoproliferative disorders. To assess the potential involvement of RARRES3 in leukemogenesis, we examined 24 cases of B-CLL, 10 of acute lymphocytic leukemia (ALL) and five related cell lines by RT-PCR and sequence analyses. We report a correlation between RARRES3 down-regulation and B-CLL progression. We also found decreased RARRES3 gene levels in ALL cases and in the five cell lines studied. We did not find mutations in any of the leukemia samples assayed, including those with 11q23 deletion. These results indicate that RARRES3 may play a role in B-CLL progression.
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Acknowledgements
This work was supported by grants SAF97-0064-CO3-02 (to AGP) and SAF97-0064-CO3-03 (to AS) from the Comisión Interministerial de Ciencia y Tecnología (CICYT); 08.1/0028/99 (to AGP) and 08.1/012/97 (to AS and AGP) from the Comunidad Autónoma de Madrid (CAM). B Casanova, MT de la Fuente and L Sanz were supported by fellowships from CAM; M García-Gila was supported by a fellowship from CICYT. We thank Drs Felipe Prosper and M José Terol (Hospital Clinico Universitario, Valencia, Spain) and Dr Ernesto Roldán (Hospital Ramón y Cajal, Madrid, Spain) for some of the samples and clinical data of B-CLL patients; Dr Santiago Rodríguez de Córdoba for critical reading of the manuscript and Ms Mercedes Hemández del Cerro for excellent technical assistance.
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Casanova, B., de la Fuente, M., Garcia-Gila, M. et al. The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression. Leukemia 15, 1521–1526 (2001). https://doi.org/10.1038/sj.leu.2402243
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DOI: https://doi.org/10.1038/sj.leu.2402243
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