Assuntos
Hemangioblastos/citologia , Células-Tronco Hematopoéticas/citologia , Mastócitos/citologia , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Citocinas/farmacologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Expressão Gênica , Hemangioblastos/efeitos dos fármacos , Hemangioblastos/metabolismo , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Imunofenotipagem , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Receptores de IgE/genética , Receptores de IgE/metabolismoRESUMO
MicroRNAs (miRs) play a key role in the pathogenesis of human malignancies and particularly in acute myeloid leukemias (AMLs) and are increasingly recognized as potential biomarkers and therapeutic targets. miR-21 is dysregulated in several types of cancers, including some hematologic malignancies, and plays a key role in carcinogenesis, disease recurrence and metastasis. However, no studies have specifically investigated the role of miR-21 in AMLs. In this study we analyzed the expression of miR-21 and of its target PDCD4 (Programmed Cell Death 4) during normal hematopoietic differentiation and in AMLs. Our results showed that: (i) miR-21 expression is strongly up-modulated during normal granulo/monocytic differentiation, while PDCD4 protein level is concomitantly downmodulated; (ii) miR-21 is frequently overexpressed in AML blasts, in association with a marked PDCD4 protein downmodulation; (iii) miR-21 expression level is particularly elevated in NPM1mutant AMLs. Together, these findings suggest that deregulated miR-21 expression may contribute to disease pathogenesis in NPM1-mutated AMLs.
