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MEIS 1 expression is downregulated through promoter hypermethylation in AML1-ETO acute myeloid leukemias

Leukemia volume 18, pages 1231–1237 (2004)Cite this article

Abstract

Retroviral insertional mutagenesis in BXH2 mice commonly induces myeloid leukemias. One of the most frequently involved genes in experimental studies is Meis 1. In contrast to other genes in murine models, Meis 1 has not been affected by recurrent chromosomal translocations or point mutations in human leukemias. We found a constant downregulation of the Meis 1 gene mRNA in AML1-ETO acute myeloid leukemias and in those cases harboring in frame mutations in the bZIP domain of CEBPα. The absence of the Meis 1 mRNA was not caused by inactivating point mutations in the coding sequence. Promoter hypermethylation was present in more than half of the cases (9/14), including samples obtained from the widely employed Kasumi-1 cell line. Double treatment with 5-Aza-2′-deoxycytidine and trichostatin A of the Kasumi-1 cell line partially reverses Meis 1 inhibition. HoxA9 levels were also low. In a cell line model (U937 Tet AML1-ETO), AML1-ETO expression was not associated with Meis 1 suppression at 72 h. Nevertheless, Meis 1 repression is dependent on the AML1-ETO transcript levels in treated leukemic patients. Chimeric products that arise from chromosomal translocations may be associated with locus-specific epigenetic inactivation. It remains to be investigated when this methylation process is acquired and which are the basic mechanisms underlying these molecular events in AML1-ETO and CEBPα-mutated AML.

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Acknowledgements

This study was supported by grants from the Fondo de Investigaciones Sanitarias (FIS) (PI020509 and GO3/10). U937 Tet AML1-ETO cell line was kindly provided by Dr DE Zhang, Scripps Research Institute, La Jolla, CA.

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  1. Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    A Lasa, M J Carnicer, A Aventín, C Estivill, S Brunet, J Sierra & J F Nomdedéu

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  1. A Lasa
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  2. M J Carnicer
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  3. A Aventín
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Correspondence to J F Nomdedéu.

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Lasa, A., Carnicer, M., Aventín, A. et al. MEIS 1 expression is downregulated through promoter hypermethylation in AML1-ETO acute myeloid leukemias. Leukemia 18, 1231–1237 (2004). https://doi.org/10.1038/sj.leu.2403377

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