MicroRNA profiling of paediatric AML with FLT-ITD or MLL-rearrangements: expression signatures and in-vitro modulation of miR-221/222 with BRD4/HATs inhibitors.

ABSTRACT: Novel therapeutic strategies are needed for paediatric patients affected by Acute Myeloid Leukaemia (AML), especially for high-risk patients, characterized by high relapse incidence. MicroRNAs (miRs) have been extensively studied as biomarkers in cancer and haematological disorders, and their expression has been correlated to the presence of recurrent molecular abnormalities, expression of oncogenes, as well as to prognosis/clinical outcome. In this work, we identified different miRs expression signatures related both to presence of MLL and FLT3-ITD rearrangements and to paediatric AML patients clinical outcome. Notably, miR-221/222 resulted as a possible relapse-risk related miR. Thus, we investigated miR-221/222 expression modulation by using BRD4 and HAT inhibitors (JQ1 and curcumin), alone or in association. JQ1 modulates miR 221/222 expression in AML with a synergic effect when associated with curcumin. Moreover, we observed changes in the expression of CDKN1B, a known target of miR-221/222, increase in apoptosis and impaired colony forming capacity of AML cell lines and CD34+ AML primary cultures. Altogether, these findings suggest that several miRs expression signatures may be potentially useful as risk stratification indicators and relapse prediction markers of paediatric AML. Epigenetic drugs, deserving additional research for enhancing activity, bioavailability and safety, could represent a novel therapeutic strategy for high-risk paediatric AML patients

ORGANISM(S): Homo sapiens

PROVIDER: GSE209871 | GEO | 2022/07/30

REPOSITORIES: GEO