{"id":92143,"date":"2009-10-03T00:00:00","date_gmt":"2009-10-03T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/analisis-de-los-mecanismos-patogeneticos-de-transformacion-mediados-por-bcr-abl1-y-del-desarrollo-de-resistencia-al-tratamiento-con-imatinib-en-la-leucemia-mieloide-cronica\/"},"modified":"2009-10-03T00:00:00","modified_gmt":"2009-10-03T00:00:00","slug":"analisis-de-los-mecanismos-patogeneticos-de-transformacion-mediados-por-bcr-abl1-y-del-desarrollo-de-resistencia-al-tratamiento-con-imatinib-en-la-leucemia-mieloide-cronica","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/genetica\/analisis-de-los-mecanismos-patogeneticos-de-transformacion-mediados-por-bcr-abl1-y-del-desarrollo-de-resistencia-al-tratamiento-con-imatinib-en-la-leucemia-mieloide-cronica\/","title":{"rendered":"An\u00e1lisis de los mecanismos patogen\u00e9ticos de transformaci\u00f3n mediados por bcr-abl1 y del desarrollo de resistencia al tratamiento con imatinib en la leucemia mieloide cr\u00f3nica"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Edurne San Jos\u00e9 En\u00e9riz <\/strong><\/h2>\n<p>Analysis of bcr-abl1 mediated pathogenetic mechanisms of transformation and im resistance mechanisms in chronic myeloid leukemia  chronic myeloid leukemia (cml) is a clonal disorder of the haematopoietic stem cell, in which the reciprocal translocation t(9;22)(q34;q11) generates the philadelphia chromosome and forms the fusion oncogene bcr-abl1. The development of the bcr-abl1 tyrosine kinase inhibitor imatinib mesylate (im) has revolutioned the treatment of cml disease. However, despite the clinical success obtained with the use of im, resistances and molecular evidence of persistant disease have been observed in a proportion of im treated patients. Thus, we have centered in better knowing the biology of the cml in order to identify new signal transduction pathways and determine new im resistance mechanisms, with the final aim of finding new therapeutic targets in cml. In this way, we have described a new signal transduction pathway hspa8-ccnd1 implicated in the abnormal proliferation of cml cells. In the second place, we have identified four drug transporter genes (abcc4, abca3, abcg2 and slc22a13) and 19 micrornas whose expression profile may predict clinical resistance to im in patients with newly diagnosed cml. Moreover, abcc4 overexpression might constitute a mechanism of resistance to im treatment. In the same way, bim underexpression in cml patients, at least partially regulated by gene promoter methylation, is associated with reduced optimal responses to im treatment in cml. Finally, from all the studies carried out in this thesis, we have identified several therapeutic targets such as hspa8, suggesting the combination of im and a hspa8 inhibitor (15-deoxyspergualin) for those cml patients with hspa8 overexpression. Another therapeutical target is abcc4, suggesting the combination of im with abcc4 inhibitors (diclofenac and dypiridamole) for cml patients with abcc4 overexpression and resistance to im treatment. Finally, we have also identified bim as a new therapeutic target in cml, suggesting the combination of im with a demethylating agent decitabine as a new therapeutic strategy for patients with cml and hypermethylation of the bim promoter.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>An\u00e1lisis de los mecanismos patogen\u00e9ticos de transformaci\u00f3n mediados por bcr-abl1 y del desarrollo de resistencia al tratamiento con imatinib en la leucemia mieloide cr\u00f3nica<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 An\u00e1lisis de los mecanismos patogen\u00e9ticos de transformaci\u00f3n mediados por bcr-abl1 y del desarrollo de resistencia al tratamiento con imatinib en la leucemia mieloide cr\u00f3nica <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Edurne San Jos\u00e9 En\u00e9riz <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 10\/03\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Felipe Luis Prosper Cardoso<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 Antonio Paramo fernandez <\/li>\n<li>Juan  cruz Cigudosa garcia (vocal)<\/li>\n<li>josep Mar\u00eda Ribera santasusana (vocal)<\/li>\n<li>Jos\u00e9 Rom\u00e1n g\u00f3mez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Edurne San Jos\u00e9 En\u00e9riz Analysis of bcr-abl1 mediated pathogenetic mechanisms of transformation and im resistance mechanisms in [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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