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Differentiation

Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture

Leukemia volume 23, pages 753–760 (2009)Cite this article

Abstract

Jasmonates are potent lipid regulators in plants that play pivotal roles in their biological activities. Methyl jasmonate (MJ) is very effective at inducing the myelomonocytic differentiation of human myeloid leukemia HL-60 cells. We examined the gene expression profiles associated with exposure to MJ using cDNA microarrays, and compared the results with those obtained with other inducers of differentiation, such as all-trans retinoic acid (ATRA), 1α,25-dihydroxyvitamin D3 (VD3), isopentenyladenine (IPA) and cotylenin A (CN-A). Many genes were upregulated, and only a small fraction was downregulated, upon exposure to the inducers. MJ, IPA and CN-A, but not ATRA or VD3, immediately induced the expression of mRNA for the calcium-binding protein S100P. The gene expression profile induced by MJ resembled that induced by IPA, suggesting that these inducers share many common signal transduction systems for inducing the differentiation of leukemia cells. Methyl 4,5-didehydrojasmonate was about 30 times more potent than MJ and the natural form of the stereoisomer was more effective than the unnatural isomer. It significantly stimulated both the functional and morphological differentiation of leukemia cells that had been freshly isolated from patients with hematological malignancies. Jasmonate derivatives may be promising therapeutic agents for differentiation therapy of leukemia.

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Authors and Affiliations

  1. Department of Life Science, Shimane University School of Medicine, Izumo, Shimane, Japan

    H Tsumura, M Akimoto & Y Honma

  2. Cancer Center, Shimane University School of Medicine, Izumo, Shimane, Japan

    H Tsumura & H Ishikura

  3. Division of Bioscience and Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan

    H Kiyota

  4. Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA

    Y Ishii

Authors
  1. H Tsumura
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  2. M Akimoto
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  3. H Kiyota
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  4. Y Ishii
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  5. H Ishikura
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  6. Y Honma
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Correspondence to Y Honma.

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

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Tsumura, H., Akimoto, M., Kiyota, H. et al. Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture. Leukemia 23, 753–760 (2009). https://doi.org/10.1038/leu.2008.347

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