Chronic Myeloid Leukemia (CML) is a progressive myeloproliferative disorder accounting for about 20% of all leukemia cases in adults. The hallmark of the disease is the presence of BCR/ABL fusion gene, that in turn translates into the Bcr-Abl p210 protein. The aberrant function of Bcr-Abl p210 trigger both hematopoietic cell transformation and disease maintenance. The Bcr-Abl p210 chimeric protein is targeted by the kinase inhibitor (TKI) imatinib and its use has substantially improved the prognosis in CML patients however, the development of mutations in the ABL kinase domain often result in drug resistance particularly for the gatekeeper T315I. In the past few years, natural products gained attention because of its potential effects to prevent cancer or to diminish the risk of tumor development and in this concern, the anti-proliferative properties of bioactive components of Cynara cardunculus extracts are well known. This chapter is a focus on the medicinal chemistry and pharmacology of the sesquiterpene lactone cynaropicrin and its deacyl derivate that negatively regulate bcr BCR/ABL fusion oncogene expression, thus paving the way for a novel therapeutic strategy aimed to both potentiate the effectiveness of imatinib or of its analogues and to delay or overcome the occurrence of resistance CML chemotherapy

Sesquiterpene Lactone Cynaropicrin as Novel Inhibitor of Bcr-Abl Fusion Oncogene Expression

Caroleo, Maria Cristina;Aiello, Francesca;Cione, Erika;Di Gioia, Maria Luisa
2019

Abstract

Chronic Myeloid Leukemia (CML) is a progressive myeloproliferative disorder accounting for about 20% of all leukemia cases in adults. The hallmark of the disease is the presence of BCR/ABL fusion gene, that in turn translates into the Bcr-Abl p210 protein. The aberrant function of Bcr-Abl p210 trigger both hematopoietic cell transformation and disease maintenance. The Bcr-Abl p210 chimeric protein is targeted by the kinase inhibitor (TKI) imatinib and its use has substantially improved the prognosis in CML patients however, the development of mutations in the ABL kinase domain often result in drug resistance particularly for the gatekeeper T315I. In the past few years, natural products gained attention because of its potential effects to prevent cancer or to diminish the risk of tumor development and in this concern, the anti-proliferative properties of bioactive components of Cynara cardunculus extracts are well known. This chapter is a focus on the medicinal chemistry and pharmacology of the sesquiterpene lactone cynaropicrin and its deacyl derivate that negatively regulate bcr BCR/ABL fusion oncogene expression, thus paving the way for a novel therapeutic strategy aimed to both potentiate the effectiveness of imatinib or of its analogues and to delay or overcome the occurrence of resistance CML chemotherapy
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/309103
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