Myc-p27 expression and interactions in chronic lymphocytic leukemia and in myeloid cells differentiation

• Autores: Juan Manuel Caraballo Otero
• Directores de la Tesis: Javier León Serrano (dir. tes.)
• Lectura: En la Universidad de Cantabria ( España ) en 2013
• Idioma: inglés
• Tribunal Calificador de la Tesis: Dolors Colomer Pujol (presid.), María Teresa Gómez Casares (secret.), Ramón Merino Pérez (voc.)
• Materias:
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en:  Digital CSIC  UCrea 
• Resumen

  • [EN]: We studied expression levels of cell cycle inhibitor p27 and Myc (an oncogenic transcription factor) in more than 100 chronic lymphocytic leukemia (CLL) patients. p27 and Myc levels were inversely correlated. Thus, the ratio between p27 (overexpressed) and Myc (downregulated) appears inverted in CLL with respect to the other tumors so far known. Moreover, low p27 and high Myc expression correlated with the expression of Skp2, which is the main responsible for p27 degradation, suggesting a pathway Myc-Skp2-p27 in CLL. To investigate why p27 is expressed in CLL we overexpressed it in a CLL-derived cell line (MEC1) and observed that high levels of p27 provide resistance to fludarabine treatment. Also, we studied the erythroid differentiation in human K562 cells induced by two different p27 mutants (p27CK- and p27 Nt). p27 Nt transfection resulted in erythroid differentiation, but p27CK- only induced differentiation when Myc expression was low. Thus, we studied the correlation between both Myc and p27 in this process and we found that p27 induced erythroid differentiation through Myc downregulation.