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.
Riccioni, R., Lulli, V., Castelli, G., Biffoni, M., Tiberio, R., Pelosi, E., et al. (2015). MiR-21 is overexpressed in NPM1-mutant acute myeloid leukemias. LEUKEMIA RESEARCH, 39(2), 221-228 [10.1016/j.leukres.2014.11.001].
MiR-21 is overexpressed in NPM1-mutant acute myeloid leukemias
LO COCO, FRANCESCO;
2015-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.