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Acute Non-Lymphocytic Leukemias

Expression and methylation status of the FHIT gene in acute myeloid leukemia and myelodysplastic syndrome

Leukemia volume 19, pages 1367–1375 (2005)Cite this article

Abstract

To clarify the role of fragile histidine triad (FHIT) in hematological malignancies, we examined the methylation status and the expression level of the FHIT gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cells in comparison with the methylation of the p15INK4B gene. The FHIT methylation was found in 13 of 94 (13.8%) AML and 22 of 40 (55.0%) MDS cases, but not in normal mononuclear cells (MNCs). Both the frequency and density of methylation increased in the advanced-stages MDS and the relapsed AML cases. Although FHIT and p15INK4B methylations were not correlated in MDS and AML, increased FHIT methylation at the relapse in AML was associated with p15INK4B methylation. The median expression level in AML was significantly higher than in normal MNCs, although the median expression level in those with methylation was significantly lower than in those without methylation. Furthermore, the methylation level at relapse was significantly higher than at diagnosis in AML. These results suggested that FHIT methylation was accumulated through the disease progression of MDS and AML, and the role of the FHIT gene as a tumor suppressor seemed different in AML and MDS.

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Acknowledgements

This work was supported by Grants-in-Aid from the Japanese Ministry of Health, Labor and Welfare, Clinical Research for Evidenced Based Medicine and the Ministry of Education, Culture, Sports, Science and Technology, Scientific Research. We thank Dr Manabu Ninomiya, Ms Kyoko Aoyama, Ms Rie Ueda, Ms Satomi Yamaji and Ms Manami Kira for technical and secretarial assistance.

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Authors and Affiliations

  1. Department of Infectious Diseases, Nagoya university Graduate School of Medicine, Nagoya, Japan

    M Iwai, H Kiyoi & K Ozeki

  2. Department of Hematology, Nagoya university Graduate School of Medicine, Nagoya, Japan

    K Ozeki, T Kinoshita, N Emi & T Naoe

  3. Aichi Cancer Center, Nagoya, Japan

    R Ohno

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  1. M Iwai
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  2. H Kiyoi
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  3. K Ozeki
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Correspondence to H Kiyoi.

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Iwai, M., Kiyoi, H., Ozeki, K. et al. Expression and methylation status of the FHIT gene in acute myeloid leukemia and myelodysplastic syndrome. Leukemia 19, 1367–1375 (2005). https://doi.org/10.1038/sj.leu.2403805

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