Format

Send to

Choose Destination
See comment in PubMed Commons below
Leuk Res. 2013 Jun;37(6):647-56. doi: 10.1016/j.leukres.2013.02.019. Epub 2013 Mar 20.

MicroRNA profiling reveals aberrant microRNA expression in adult ETP-ALL and functional studies implicate a role for miR-222 in acute leukemia.

Author information

1
Hematology and Oncology, Charité, University Hospital Benjamin Franklin, Berlin, Germany.

Abstract

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup in acute T-cell lymphoblastic leukemia (T-ALL). To investigate the immature and myeloid nature of ETP-ALL we examined global microRNA (miRNA) expression in adult ETP-ALL. miRNA profiling of ETP-ALL (n=8), non-ETP T-ALL (n=6), and healthy controls was performed and results were validated in independent cohorts of 66 ETP-ALL and 111 non-ETP T-ALL using real-time RT-PCR. Furthermore, in vitro studies were performed on deregulated miRNAs in acute leukemia. We identified miR-221 and miR-222 as the most upregulated and six miRNAs (miR-151-3p, miR-19a, miR-20b, miR-342-3p, miR-363, and miR-576-3p) as downregulated in ETP-ALL compared to non-ETP T-ALL. In the validation cohorts, miR-221 and miR-222 were significantly upregulated in ETP-ALL, and miR-363 and miR-19a were downregulated in ETP-ALL. ETS1, downregulated in ETP-ALL, was identified as direct target of miR-222. In our in vitro studies miR-222 significantly inhibited proliferation, and caused cell cycle arrest and apoptosis in leukemic cells. In conclusion, our study revealed aberrant miRNA expression in ETP-ALL, with miR-221 and miR-222 as the most overexpressed miRNAs and implied a functional role for miR-222 in leukemic cells. Importantly, miR-222 may impact leukemogenesis by altering expression of the proto-oncogene ETS1 in acute leukemia.

PMID:
23522449
DOI:
10.1016/j.leukres.2013.02.019
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center