Vitamin K2 modulates differentiation and apoptosis of both myeloid and erythroid lineages

Eriko Sada, Yasunobu Abe, Rie Ohba, Yoshimichi Tachikawa, Eriko Nagasawa, Motoaki Shiratsuchi, Ryoichi Takayanagi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Vitamin K2 (VK2) can improve cytopenia in some patients with myelodysplastic syndrome (MDS). Although it is well known that VK2 induces differentiation and apoptosis in acute myeloid leukemia (AML) cell lines, little is known about its effect on normal hematopoietic progenitors. The effects of VK2 on primary myeloid and erythroid progenitors were examined. Mobilized CD34-positive cells from peripheral blood were used for the examination of myeloid lineage cells, and erythroid progenitors purified from peripheral blood were used for erythroid lineage cells. VK2 upregulated the expressions of myeloid markers CD11b and CD14, and increased the mRNA expression levels of CCAAT/enhancer binding protein-α (C/EBPα) and PU.1 in myeloid progenitors. In erythroid progenitors, VK2 did not show a significant effect on differentiation. However, VK2 exhibited an anti-apoptotic effect on erythroid progenitors under erythropoietin depletion. This anti-apoptotic effect was restricted to normal erythroid progenitors and was not shown in erythroleukemic cell line AS-E2. Steroid and xenobiotic receptor (SXR), which was recently identified as a receptor of VK2, was expressed on myeloid progenitors, and the SXR agonist rifampicin (RIF) also upregulated CD11b and CD14 expressions on myeloid progenitors. These results indicate that SXR is involved in the effect of VK2 on myeloid progenitors. The major effect of VK2 on myeloid progenitors was promoting differentiation, whereas its anti-apoptotic effect seemed to be dominant in erythroid progenitors. Although the detailed mechanism of VK2's effect on differentiation or apoptosis of hematopoietic progenitors remains unknown, the effect of VK2 therapy in patients with MDS could be partly explained by these mechanisms.

Original languageEnglish
Pages (from-to)538-548
Number of pages11
JournalEuropean Journal of Haematology
Volume85
Issue number6
DOIs
Publication statusPublished - Dec 2010

All Science Journal Classification (ASJC) codes

  • Hematology

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