Guangshan Tan1, Lei Shi1, Qiang Li2, Mingjun Wang2. 1. Department of Pharmacy, People's Hospital of Liaocheng, Shandong, 252000, China. 2. Department of Hematology, People's Hospital of Liaocheng, Shandong, 252000, China.
Abstract
OBJECTIVES: Adiponectin, a functional ligand of adiponectin receptor-1 (AdipoR1) and adiponectin receptor-2 (AdipoR2), has been found to be linked to risk of development of chronic myeloid leukaemia (CML). Imatinib, as its first-line therapy, exhibits striking activity in both chronic and accelerated phases of the condition. However, numerous clinical trials have shown that many patients become refractory or experience relapses. Thus, development of new, hopefully effective Imatinib-based treatment strategies, are still needed. MATERIALS AND METHODS: Effects of recombinant adiponectin protein, in enhancing Imatinib anti-tumour activities, in K562 and MEG-01 CML cells, were examined in vitro and in vivo. Forty-eight consecutive newly diagnosed adult patients with Bcr-Abl-positive CML, in the early chronic phase (ECP), were enrolled in the study. Imatinib efficacy, plasma adiponectin levels and their correlations were analysed. RESULTS: Data presented here indicate that adiponectin enhanced Imatinib efficacy in vitro and in vivo. Furthermore, this augmented effect was due to inhibition of Bcr-Abl tyrosine kinase activity in an AdipoR1-dependent way, while AdipoR2 was not involved. Most importantly, additional clinical data revealed that adiponectin plasma levels in CML ECP patients, correlated with Imatinib efficacy. CONCLUSIONS: Adiponectin enhanced Imatinib anti-tumour activity in human chronic myeloid leukaemia cells and its serum levels were associated with Imatinib efficacy, in early chronic phase patients.
OBJECTIVES:Adiponectin, a functional ligand of adiponectin receptor-1 (AdipoR1) and adiponectin receptor-2 (AdipoR2), has been found to be linked to risk of development of chronic myeloid leukaemia (CML). Imatinib, as its first-line therapy, exhibits striking activity in both chronic and accelerated phases of the condition. However, numerous clinical trials have shown that many patients become refractory or experience relapses. Thus, development of new, hopefully effective Imatinib-based treatment strategies, are still needed. MATERIALS AND METHODS: Effects of recombinant adiponectin protein, in enhancing Imatinib anti-tumour activities, in K562 and MEG-01 CML cells, were examined in vitro and in vivo. Forty-eight consecutive newly diagnosed adult patients with Bcr-Abl-positive CML, in the early chronic phase (ECP), were enrolled in the study. Imatinib efficacy, plasma adiponectin levels and their correlations were analysed. RESULTS: Data presented here indicate that adiponectin enhanced Imatinib efficacy in vitro and in vivo. Furthermore, this augmented effect was due to inhibition of Bcr-Abl tyrosine kinase activity in an AdipoR1-dependent way, while AdipoR2 was not involved. Most importantly, additional clinical data revealed that adiponectin plasma levels in CML ECP patients, correlated with Imatinib efficacy. CONCLUSIONS:Adiponectin enhanced Imatinib anti-tumour activity in humanchronic myeloid leukaemia cells and its serum levels were associated with Imatinib efficacy, in early chronic phase patients.
Authors: David J Barnes; Danai Palaiologou; Eleni Panousopoulou; Beate Schultheis; Agnes S M Yong; Alice Wong; Laura Pattacini; John M Goldman; Junia V Melo Journal: Cancer Res Date: 2005-10-01 Impact factor: 12.701
Authors: Mei Huang; Jay F Dorsey; P K Epling-Burnette; Ramadevi Nimmanapalli; Terry H Landowski; Linda B Mora; Guilian Niu; Dominic Sinibaldi; Fanqi Bai; Alan Kraker; Hua Yu; Lynn Moscinski; Sheng Wei; Julie Djeu; William S Dalton; Kapil Bhalla; Thomas P Loughran; Jie Wu; Richard Jove Journal: Oncogene Date: 2002-12-12 Impact factor: 9.867