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神戸マラソンに約2万人 健脚競う (NHK)

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Evaluation of cooperative anti-leukemic effects of nilotinib and vildagliptin in Ph(+) chronic myeloid leukemia.

著者 Willmann M , Sadovnik I , Eisenwort G , Entner M , Bernthaler T , Stefanzl G , Hadzijusufovic E , Berger D , Herrmann H , Hoermann G , Valent P , Rülicke T
Exp Hematol.2017 Oct 12 ; ():.
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Chronic myeloid leukemia (CML) is a stem cell neoplasm characterized by the BCR/ABL1 oncogene. Although the disease can be kept under control using BCR/ABL1 tyrosine kinase inhibitors (TKI) in most cases, some patients relapse or have resistant disease which points to the need to identify new therapeutic targets in this malignancy. Recent data suggest that leukemic stem cell (LSC) in CML display the SC-mobilizing cell surface enzyme dipeptidyl-peptidase IV (DPPIV=CD26) in an aberrant manner. In the present study, we analyzed the effects of the DPPIV blocker vildagliptin as single agent or in combination with the BCR/ABL1 TKI imatinib or nilotinib on growth and survival of CML LSC in vitro and on LSC engraftment in an in vivo xenotransplantation NSG mouse model. We found that nilotinib induces apoptosis in CML LSC and inhibits their engraftment in NSG mice. By contrast, no substantial effects were seen with imatinib or vildagliptin. Nevertheless, vildagliptin was found to reduce the 'mobilization' of CML LSC from a stroma cell layer consisting of mouse fibroblasts in an in vitro co-culture model, suggesting reduced disease expansion. However, although vildagliptin and nilotinib produced cooperative effects in individual experiments, overall, no significant effects of co-administered vildagliptin over nilotinib or imatinib treatment alone on engraftment of CML cells in NSG mice were seen. Together, gliptins may be interesting drugs in the context of CML and nilotinib therapy, but our preclinical studies did not reveal a major cooperative effect of the drug-combination 'vildagliptin+nilotinib' on engraftment of CML cells in NSG mice.
PMID: 29031704 [PubMed - as supplied by publisher]
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