Estudio de los mecanismos de resistencia asociados al tratamiento con inhibidores de tirosina kinasas en leucemias philadelphia positivas
The resistance to treatment in Chronic Myeloid Leukemia may be due, between others, to mutations in the BCR-ABL1, overexpression of Src-kinases or down-regulation of onco-suppressors genes. The presence of the BCR-ABL1 in Acute Lymphoblastic Leukemia (ALL) is associated with poor prognosis; therefor...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_814 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_814.dir/814.PDF |
| Aporte de: |
| Sumario: | The resistance to treatment in Chronic Myeloid Leukemia may be due, between others, to mutations in the BCR-ABL1, overexpression of Src-kinases or down-regulation of onco-suppressors genes. The presence of the BCR-ABL1 in Acute Lymphoblastic Leukemia (ALL) is associated with poor prognosis; therefore more aggressive protocols were developed including tyrosine kinase inhibitors (TKI).\nThe hypothesis of this study was to determine if early mutations detection in BCR-ABL1, and expression of LYN and PTEN genes would be involved in treatment resistance.\nUsing high resolution melting and ARMS-qPCR the detection of mutations was increased in 16% with respect to direct sequencing. The analysis of dynamics of mutated clone and the BCR-ABL1 transcripts, allowed to define the role of mutation in the resistance, selecting the appropriate TKI and to evaluate treatment response.\nThe analysis of LYN/PTEN expression in imatinib or nilotinib resistant patients without mutations, allowed associating the lack of response to treatment with altered expression of these genes.\nThe quantification of BCR-ABL1P190 in ALL, proved to be an important tool to evaluate treatment response and define minimum residual disease prior to bone marrow transplantation. |
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