title: Can anthocyanins improve maintenance therapy of Ph(+) acute lymphoblastic leukaemia?
abstract: Chemotherapy and tyrosine kinase inhibitors provide high remission rates. However, prognosis of adult patients with Philadelphia chromosome-positive 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.
authors.affiliation: Department of Paediatrics, UKSH, Campus Lübeck, Universität zu Lübeck, Ratzeburger Allee 160, Lübeck, Germany. koechling.luebeck@freenet.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Köchling
authors.forename: Manuel
authors.initials: M
authors.lastname: Schmidt
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rott
authors.forename: Michael
authors.initials: M
authors.lastname: Sagner
authors.forename: Hendrik
authors.initials: H
authors.lastname: Ungefroren
authors.forename: Burghard
authors.initials: B
authors.lastname: Wittig
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
mesh_terms: D000328:Adult; D000818:Animals; D000872:Anthocyanins / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D060046:Maintenance Chemotherapy; D051379:Mice; D008822:Mice, Transgenic; D010879:Piperazines / Q000627:therapeutic use; D010936:Plant Extracts / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: D000872:Anthocyanins; D000972:Antineoplastic Agents, Phytogenic; D001549:Benzamides; D010879:Piperazines; D010936:Plant Extracts; D011743:Pyrimidines; D019444:Vaccines, DNA; D000068877:Imatinib Mesylate; D020169:Caspases