Details

Autor(en) / Beteiligte

• Coskun, Ebru
• Neumann, Martin
• Schlee, Cornelia
• Liebertz, Frauke
• Heesch, Sandra
• Goekbuget, Nicola
• Hoelzer, Dieter
• Baldus, Claudia D

Titel

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

Ist Teil von

• Leukemia research, 2013-06, Vol.37 (6), p.647-656

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.