0000000000290256
AUTHOR
R Karmali
carboxyamidotriazole-orotate inhibits the growth of imatinib resistant chronic myeloid leukaemia cells and modulates exosomes-stimulated angiogenesis
The Bcr/Abl kinase has been targeted for the treatment of chronic myelogenous leukaemia (CML) by imatinib mesylate. Although more common in solid tumors, increased microvessel density was also reported in chronic myelogenous leukaemia and was associated with a significant increase of angiogenic factors, suggesting that vascularity in haematologic malignancies is a controlled process and may play a role in the leukaemogenic process thus representing an alternative therapeutic target. Carboxyamidotriazole-orotate (CTO) is the orotate salt form of carboxyamidotriazole (CAI), an orally bioavailable signal transduction inhibitor that in vitro has been shown to possess antileukaemic activities (1…
Tumor microenvironment modulation by exosomes in chronic myelogenous leukemia
Exosomes are small vesicles of 40-100 nm diameter that are initially formed within the endosomal compartment and are secreted when a multivesicular body (MVB) fuses with the plasma membrane. These vesicles are released by many cell types including cancer cells and are considered messengers in intercellular communication. The exact function of exosomes in malignant cells has yet to be elucidated, but investigation has suggested roles in cell-to-cell communication, tumor-stroma interaction, and antigen presentation, thus potentially affecting cancer progression at different steps. Although production of exosomes by CML cells has been reported, little is known regarding the role of these vesic…
Carboxyamidotriazole-orotate inhibits the growth of Imatinib resistantchronic myeloid leukemia cells and modulates exosomes stimulated Angiogenesis
Chronic myeloid leukemia (CML) is characterized by the expression of Bcr–Abl oncoprotein with a constitutive tyrosine kinase that drives disease pathogenesis. Imatinib is the election therapy for CML, but some patients are resistant to this drug. Recently, attention is being focused on cell-cell communication that involves membrane vesicles called exosomes. A number of studies have described exosomes as new players in modulating the tumor microenvironment, promoting angiogenesis and tumor development; furthermore neovascularization is known to exert an important role in the progression of chronic myeloid leukaemia and may represent a valid alternative target for therapy. Little is known reg…