期刊
EUROPEAN JOURNAL OF HAEMATOLOGY
卷 90, 期 4, 页码 291-300出版社
WILEY
DOI: 10.1111/ejh.12071
关键词
Ph plus acute lymphoblastic leukaemia; relapse prevention; anthocyanins; DNA vaccine
类别
资金
- Deutsche Jose-Carreras-Leukamiestiftung
- Lubeck Hilfe fur krebskranke Kinder
Chemotherapy and tyrosine kinase inhibitors provide high remission rates. However, prognosis of adult patients with Philadelphia chromosomepositive acute lymphoblastic leukaemia (Ph+ ALL) still remains poor. Because most adults eventually relapse without allogeneic stem cell transplantation, which is not available for all patients, novel strategies are required for relapse prevention. As the integrity of the immune system is essential for the control of remaining leukaemia cells, we compared the efficacy of anthocyanins, imatinib and a DNA-based vaccine as non-immunosuppressant components with 6-mercaptopurine (6-MP) to control minimal residual disease in vitro and in vivo using different leukaemia cell lines and syngeneic mice. Proliferation of Ph+ ALL was significantly better inhibited by anthocyanin-rich berry extract or imatinib compared with 6-MP. Although anthocyanins induced apoptosis in some leukaemia cell lines, the level of caspase-3, caspase-8 and caspase-9 was significantly lower compared with imatinib and 6-MP. When used as single components, anthocyanins and imatinib mesylate failed to eradicate pre-existing Ph+ ALL in syngeneic mice, while 6-MP led to 10% and DNA vaccination to 56% survival. Intriguingly, only the combination of DNA vaccination with berry extract but not with the isolated anthocyanin, cyanidin-3-rutinoside or imatinib further increased leukaemia-free and overall survival, and 90% of lethally challenged mice survived. We suggest that induction and enhancement of a leukaemia-specific immunity by DNA vaccination and anthocyanin-rich berry extract can also decrease the relapse rate in patients with Ph+ ALL. Furthermore, this approach may serve as strategy for maintenance therapy of other malignancies.
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