Effect of phenylhexyl isothiocyanate on aberrant histone H3 methylation in primary human acute leukemia.

Abstract

BACKGROUND:

We have previously studied the histone acetylation in primary human leukemia cells. However, histone H3 methylation in these cells has not been characterized.

METHODS:

This study examined the methylation status at histone H3 lysine 4 (H3K4) and histone H3 lysine 9 (H3K9) in primary acute leukemia cells obtained from patients and compared with those in the non-leukemia and healthy cells. We further characterized the effect of phenylhexyl isothiocyanate (PHI), Trichostatin A (TSA), and 5-aza-2'-deoxycytidine (5-Aza) on the cells.

RESULTS:

We found that methylation of histone H3K4 was virtually undetectable, while methylation at H3K9 was significantly higher in primary human leukemia cells. The histone H3K9 hypermethylation and histone H3K4 hypomethylation were observed in both myeloid and lymphoid leukemia cells. PHI was found to be able to normalize the methylation level in the primary leukemia cells. We further showed that PHI was able to enhance the methyltransferase activity of H3K4 and decrease the activity of H3K9 methyltransferase. 5-Aza had similar effect on H3K4, but minimal effect on H3K9, whereas TSA had no effect on H3K4 and H3K9 methyltransferases.

CONCLUSIONS:

This study revealed opposite methylation level of H3K4 and H3K9 in primary human leukemia cells and demonstrated for the first time that PHI has different effects on the methyltransferases for H3K4 and H3K9.

• Authors: Yong Zou, Xudong Ma, Yiqun Huang, Lingling Hong, Jen-wei Chiao
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 5 Pg. 36 (Jul 02 2012) ISSN: 1756-8722 [Electronic] England
• PMID: 22747680 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Histone Deacetylase Inhibitors
• Histones
• Hydroxamic Acids
• Isothiocyanates
• 6-phenylhexyl isothiocyanate
• trichostatin A
• Decitabine
• Histone-Lysine N-Methyltransferase
• Azacitidine

Topics

• Acetylation (drug effects)
• Acute Disease
• Adolescent
• Adult
• Aged
• Antimetabolites, Antineoplastic (pharmacology)
• Azacitidine (analogs & derivatives, pharmacology)
• Case-Control Studies
• Child
• DNA Methylation (drug effects)
• Decitabine
• Female
• Histone Deacetylase Inhibitors (pharmacology)
• Histone-Lysine N-Methyltransferase (antagonists & inhibitors, metabolism)
• Histones (genetics)
• Humans
• Hydroxamic Acids (pharmacology)
• Isothiocyanates (pharmacology)
• Leukemia (genetics)
• Male
• Middle Aged
• Protein Processing, Post-Translational
• Young Adult