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Molecular Targets for Therapy

Aberrant DNA methylation of the Src kinase Hck, but not of Lyn, in Philadelphia chromosome negative acute lymphocytic leukemia

Leukemia volume 21, pages 906–911 (2007)Cite this article

Abstract

Hck and Lyn are required in Philadelphia chromosome (Ph) positive acute lymphocytic leukemia (ALL). Here, we present evidence that the promoter CpG island of Hck, but not of Lyn, is aberrantly methylated in leukemia. Hck promoter DNA methylation was detected in 13 out of 23 (56.5%) hematopoietic and eight out of 10 (80%) non-hematopoietic cell lines, but not in normal controls. Treatment with 5-aza-2′-deoxycytidine induced demethylation and restoration of Hck mRNA and protein expression. Hck methylation (⩾15%) was detected in nine out of 44 (20%) patients with Ph negative ALL, and in one out 16 (6%) patients with Ph positive ALL, but not in patients with AML or chronic myelogenous leukemia. In this subset of patients, low levels of Hck methylation (10–15%) were observed in 26–30% of patients. Lyn methylation was observed in three out of 28 (10.7%) cell lines, but only in one out of 71 (1.4%) patients. Patients with Ph negative ALL and Hck methylation had a poorer prognosis. These data indicate that Hck may have tumor suppressor properties in BCR-ABL negative leukemia.

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Acknowledgements

This work was funded in part by Grants CA100067 and CA105771 from the NCI, and the University of Texas MD Anderson Cancer Center's Physician-Scientist Program Award funded by the Commonwealth Cancer Foundation for Research (G G-M). We thank Claritza Santos-Malave, a visiting student from the University of Puerto Rico, for technical assistance, and to Drs N Donato and M Beran for sharing cell lines. DNA sequencing was performed at a core facility at the University of Texas MD Anderson Cancer funded by Core Grant CA16672.

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  1. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    K Hoshino, A Quintás-Cardama, H Yang, B Sanchez-Gonzalez & G Garcia-Manero

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  1. K Hoshino
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  2. A Quintás-Cardama
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  3. H Yang
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Correspondence to G Garcia-Manero.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Hoshino, K., Quintás-Cardama, A., Yang, H. et al. Aberrant DNA methylation of the Src kinase Hck, but not of Lyn, in Philadelphia chromosome negative acute lymphocytic leukemia. Leukemia 21, 906–911 (2007). https://doi.org/10.1038/sj.leu.2404615

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