Chronic myeloid leukemia (CML) is caused by constituve activity of BCR-ABL tyrosine kinase. Despite of high efficiency of imatinib, selective BCR-ABL inhibitor, about 30% of patients develop resistance. Novel markers and targets for therapy are thus necessary. MicroRNAs are small intereference RNAs whose role in physiological and malignant hematopoiesis has been shown. This study is focused on miR-451 in CML. Following our observation of miR-451 downregulation in CML, we further show its relation to BCR-ABL activity. Our data together with current literature indicate a more complex relationship of miR-451 and BCR-ABL in CML.

• MeSH
• bcr-abl fúzové proteiny antagonisté a inhibitory   MeSH
• chronická myeloidní leukemie genetika   MeSH
• geny abl fyziologie   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bcr-abl fúzové proteiny MeSH
• mikro RNA MeSH
• MIRN451 microRNA, human MeSH Prohlížeč

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by an abnormal fusion gene BCR-ABL. BCR-ABL encodes a constitutively active Bcr-Abl tyrosine kinase, which is required and sufficient for cellular transformation. Bcr-Abl is, therefore, an ideal target for pharmacotherapy. Imatinib Mesylate (Glivec) is a specific inhibitor of Bcr-Abl kinase. Imatinib shows high efficiency and low toxicity in treatment of CML patients. The main problem of imatinib treatment is the development of resistance. The mechanisms of resistance can be divided into two groups. The first group is characterized by reactivation of Bcr-Abl kinase in spite of continual imatinib presence. This can be caused by BCR-ABL amplification, overexpression or mutation in Abl kinase domain. Imatinib might not even reach the target Bcr-Abl protein (possible causes: drug efflux or imatinib binding to alpha1-acid glycoprotein). In the second group of resistance mechanisms, the Bcr-Abl kinase is inhibited but the resistance is maintained by other signal transducers (e.g. Src kinases). Standard cytogenetics as well as assay evaluating the phosphorylation status of Bcr-Abl substrate and/or sequencing of Abl kinase transcript can be used to test the mechanism of resistance. Treatment of patients can be re-evaluated on the basis of the status of IM resistance.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• bcr-abl fúzové proteiny MeSH
• benzamidy MeSH
• chemorezistence * MeSH
• chronická myeloidní leukemie farmakoterapie   MeSH
• geny abl fyziologie   MeSH
• imatinib mesylát MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé MeSH
• piperaziny terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• signální transdukce MeSH
• tyrosinkinasy antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• bcr-abl fúzové proteiny MeSH
• benzamidy MeSH
• imatinib mesylát MeSH
• inhibitory proteinkinas MeSH
• piperaziny MeSH
• pyrimidiny MeSH
• tyrosinkinasy MeSH