論文 - 詳細
| RRC ID | 55787 |
|---|---|
| 著者 | Kurata T, Matsuda K, Hirabayashi K, Shigemura T, Sakashita K, Nakahata T, Koike K. |
| タイトル | Panobinostat inhibits the proliferation of CD34+ CD38- cells under stimulation of hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia. |
| ジャーナル | Pediatr Blood Cancer |
| Abstract |
BACKGROUND:Encouraging responses to histone deacetylase inhibitors have been reported for hematologic malignancies. Here, we report effects of panobinostat and 5-azacytidine on the proliferation of juvenile myelomonocytic leukemia (JMML) CD34+ cells. PROCEDURE:We previously reported that stimulation of JMML CD34+ cells with stem cell factor and thrombopoietin on irradiated murine AGM-S3 cells led to substantial expansion of JMML CD34+ cells that contained leukemic stem cells capable of transplantation into immunodeficient mice. Using this culture system, we evaluated effects of panobinostat and 5-azacytidine on the proliferation of JMML CD34+ cells. RESULTS:Panobinostat dose dependently reduced the numbers of day 7 CD34+ cells generated under stimulation of hematopoietic growth factors on AGM-S3 cells in all eight patients with JMML. These patients possessed various genetic and/or karyotypic abnormalities. CD34+ CD38- cells were substantially more sensitive to panobinostat at 10 and 20 nM than CD34+ CD38+ cells. Panobinostat, however, failed to influence the ability of AGM-S3 cells to stimulate JMML CD34+ cell production. In contrast to HL60 cells, apoptosis and cell cycle arrest in panobinostat-mediated inhibition were at low levels in JMML. The inhibitor also suppressed the factor-dependent proliferation of normal CD34+ cells on AGM-S3 cells. Meanwhile, no substantial inhibitory effects of 5-azacytidine on the growth of JMML CD34+ cells were observed. CONCLUSIONS:These results demonstrate that panobinostat directly suppresses the growth of JMML CD34+ cells, in particular CD34+ CD38- cells, regardless of the genetic abnormality type, suggesting that it is a useful antileukemic drug to target JMML stem cells at a pretransplant stage. |
| 巻・号 | 65(11) |
| ページ | e27261 |
| 公開日 | 2018-11-1 |
| DOI | 10.1002/pbc.27261 |
| PMID | 30014555 |
| MeSH | Animals Antigens, CD34 Antineoplastic Agents / pharmacology* Azacitidine / pharmacology Cell Line Cell Proliferation / drug effects* Child, Preschool Hematopoietic Stem Cells Humans Infant Leukemia, Myelomonocytic, Juvenile* Male Mice Panobinostat / pharmacology* Tumor Cells, Cultured |
| IF | 2.486 |
| 引用数 | 0 |
| リソース情報 | |
| 研究用ヒト臍帯血幹細胞 | |