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ABSTRACT We have previously reported that vitamin K2 (VK2) has a potent apoptosis inducing activity toward various types of primary cultured leukemia cells including acute myelogenous

leukemia arising from myelodysplastic syndromes (MDS). We established a novel cell line, designated MDS-KZ, from a patient with MDS in blastic transformation, and further investigated the

effects of VK2 using this novel cell line. MDS-KZ shows complex chromosomal anomaly including −4, 5q−, −7, 13q+, 20q−, consistent with that seen in the original patient. Culture of MDS-KZ

cells in RPMI1640 medium containing 10% FBS lead to steady but very slow proliferation with a doubling time of 14 days. However, the cellular growth rate was significantly accelerated in the

presence of various growth factors such as granulocyte colony-stimulating factor, stem cell factor, granulocyte–macrophage colony-stimulating factor, interleukin-3, and thrombopoietin. Most

of the cultured cells show the morphological features of myeloblasts. They are positive for CD7, CD33, CD34, CD45, CD117, and HLA-DR. However, about 10% of the cells are more mature

metamyelocytes and neutrophils with various dysplastic characteristics such as pseudo-Pelger nuclear anomaly and hypersegmentation, suggesting a potential for differentiation in this cell

line. As previously reported for cultured primary leukemia cells, exposure to VK2, but not to VK1, resulted in induction of apoptosis of MDS-KZ cells in a dose-dependent manner (IC50: 5 μM).

In addition, VK2 treatment induced down-regulation of BCL-2 and up-regulation of BAX protein expression with concomitant activation of caspase-3 (CPP32). A tetrapeptide functioning as

antagonist of caspase-3, Ac-DEVD-H, suppressed the VK2-induced inhibition of cell growth, suggesting that caspase-3 is, at least in part, involved in VK2-induced apoptosis. These

observations suggest that the MDS-KZ cell line can serve as a model for the study of the molecular mechanisms of VK2-induced apoptosis. Access through your institution Buy or subscribe This

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CHANGES IN GENE EXPRESSION AND JNK ACTIVATION Article 11 June 2021 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * First Department of Internal Medicine (Hematology/Oncology), Tokyo Medical

University, Tokyo, Japan J Nishimaki, K Miyazawa, M Yaguchi, T Katagiri, Y Kawanishi, K Toyama & K Ohyashiki * Laboratory of Biological Chemistry, School of Pharmaceutical Sciences,

Showa University, Tokyo, Japan S Hashimoto & K Nakaya * Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, Kanazawa, Japan T Takiguchi

Authors * J Nishimaki View author publications You can also search for this author inPubMed Google Scholar * K Miyazawa View author publications You can also search for this author inPubMed 

Google Scholar * M Yaguchi View author publications You can also search for this author inPubMed Google Scholar * T Katagiri View author publications You can also search for this author

inPubMed Google Scholar * Y Kawanishi View author publications You can also search for this author inPubMed Google Scholar * K Toyama View author publications You can also search for this

author inPubMed Google Scholar * K Ohyashiki View author publications You can also search for this author inPubMed Google Scholar * S Hashimoto View author publications You can also search

for this author inPubMed Google Scholar * K Nakaya View author publications You can also search for this author inPubMed Google Scholar * T Takiguchi View author publications You can also

search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nishimaki, J., Miyazawa, K., Yaguchi, M. _et al._ Vitamin

K2 induces apoptosis of a novel cell line established from a patient with myelodysplastic syndrome in blastic transformation. _Leukemia_ 13, 1399–1405 (1999).

https://doi.org/10.1038/sj.leu.2401491 Download citation * Received: 18 March 1999 * Accepted: 06 May 1999 * Published: 09 September 1999 * Issue Date: 01 September 1999 * DOI:

https://doi.org/10.1038/sj.leu.2401491 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * myelodysplastic syndromes * apoptosis * vitamin K2 *

cell line