Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha
| Autor: | Rabab M, El Eit, Ahmad N, Iskandarani, Jessica L, Saliba, Mark N, Jabbour, Rami A, Mahfouz, Nizar M A, Bitar, Hanadi R El, Ayoubi, Ghazi S, Zaatari, Francois-Xavier, Mahon, Hugues B, De Thé, Ali A, Bazarbachi, Rihab R, Nasr |
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| Rok vydání: | 2013 |
| Předmět: |
Mice
Inbred BALB C Interferon-alpha Apoptosis Oxides Prognosis Real-Time Polymerase Chain Reaction Antiviral Agents Arsenicals Piperazines Survival Rate Mice Cell Transformation Neoplastic Pyrimidines Arsenic Trioxide Leukemia Myelogenous Chronic BCR-ABL Positive Antineoplastic Combined Chemotherapy Protocols Benzamides Imatinib Mesylate Tumor Cells Cultured Animals Humans Tumor Stem Cell Assay Bone Marrow Transplantation |
| Zdroj: | International journal of cancer. 134(4) |
| ISSN: | 1097-0215 |
| Popis: | Imatinib is the standard of care in chronic meloid leukemia (CML) therapy. However, imatinib is not curative since most patients who discontinue therapy relapse indicating that leukemia initiating cells (LIC) are resistant. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, improved outcome was reported with the combination of interferon and imatinib. Arsenic trioxide was suggested to decrease CML LIC. We investigated the effects of arsenic and IFN on human CML cell lines or primary cells and the bone marrow retroviral transduction/transplantation murine CML model. In vitro, the combination of arsenic and IFN inhibited proliferation and activated apoptosis. Importantly, arsenic and IFN synergistically reduced the clonogenic activity of primary bone marrow cells derived from CML patients. Finally, in vivo, combined interferon and arsenic treatment, but not single agents, prolonged the survival of primary CML mice. Importantly, the combination severely impaired engraftment into untreated secondary recipients, with some recipients never developing the disease, demonstrating a dramatic decrease in CML LIC activity. Arsenic/IFN effect on CML LIC activity was significantly superior to that of imatinib. These results support further exploration of this combination, alone or with imatinib aiming at achieving CML eradication rather than long-term disease control. |
| Databáze: | OpenAIRE |
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