| RRC ID |
39592
|
| 著者 |
Inai K, Tsutani H, Yamauchi T, Fukushima T, Iwasaki H, Imamura S, Wano Y, Nemoto Y, Naiki H, Ueda T.
|
| タイトル |
Differentiation induction in non-lymphocytic leukemia cells upon treatment with mycophenolate mofetil.
|
| ジャーナル |
Leuk Res
|
| Abstract |
Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U937 leukemic cells as well as in fresh leukemia cells from patients with non-lymphocytic leukemia. Treatment with mycophenolate mofetil reduced the intracellular guanosine 5'-triphosphate (GTP) levels and induced morphologic and functional differentiation in HL-60 and U937 cells dose-dependently. HL-60 and U937 cells developed macrophage-like cytoplasm as well as the expression of CD11b and CD14 antigens and the ability to oxidize nitroblue tetrazorium (NBT). These changes became evident when the intracellular GTP levels decreased to approximately 20-30% of the untreated control level and were abrogated by the addition of guanosine. In the fresh leukemic cells, differentiation induction was shown in the cells derived from seven of 13 patients. The fresh leukemia cells responding to mycophenolate mofetil revealed significant higher positivity to CD11b, CD14, and NBT before treatment and significantly reduced intracellular GTP levels after treatment compared to the non-responding cells. These findings suggest that mycophenolate mofetil induces differentiation in HL-60 and U937 cells and some fresh leukemia cells with moderate tendency to maturation, by causing a decrease in the intracellular GTP levels. Mycophenolate mofetil could be a promising differentiation inducer in vivo.
|
| 巻・号 |
24(9)
|
| ページ |
761-8
|
| 公開日 |
2000-9-1
|
| DOI |
10.1016/s0145-2126(00)00045-x
|
| PII |
S0145-2126(00)00045-X
|
| PMID |
10978780
|
| MeSH |
Adult
Aged
Antineoplastic Agents / pharmacology*
Cell Differentiation / drug effects*
Female
HL-60 Cells
Humans
Leukemia, Myeloid / pathology*
Male
Middle Aged
Mycophenolic Acid / analogs & derivatives*
Mycophenolic Acid / pharmacology
Myelodysplastic Syndromes / pathology*
Tumor Cells, Cultured
U937 Cells
|
| IF |
2.214
|
| 引用数 |
30
|
|
WOS 分野
|
HEMATOLOGY
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HL60(RCB0041) |
