Details

Autor(en) / Beteiligte

• Desjobert, Cécile
• Renalier, Marie-Hélène
• Bergalet, Julie
• Dejean, Emilie
• Joseph, Nicole
• Kruczynski, Anna
• Soulier, Jean
• Espinos, Estelle
• Meggetto, Fabienne
• Cavaillé, Jérome
• Delsol, Georges
• Lamant, Laurence

Titel

MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression

Ist Teil von

• Blood, 2011-06, Vol.117 (24), p.6627-6637

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• Although deregulated expression of specific microRNAs (miRNAs) has been described in solid cancers and leukemias, little evidence of miRNA deregulation has been reported in ALK-positive (ALK+) anaplastic large cell lymphomas (ALCL). These tumors overexpress the major antiapoptotic protein myeloid cell leukemia 1 (MCL-1), a situation that could compensate for the lack of BCL-2. We report that ALK+ ALCL cell lines and biopsy specimens (n = 20) express a low level of miR-29a and that this down-modulation requires an active NPM-ALK kinase. Murine models (transgenic mice and mouse embryonic fibroblast [MEF] cells), which allow conditional NPM-ALK fusion protein expression, showed an increase of miR-29a expression in the absence of NPM-ALK. Concordant results were observed after the abolition of NPM-ALK kinase activity (siALK or PF-2341066) in NPM-ALK+ ALCL cell lines. In addition, we showed that low expression of miR-29a, probably through methylation repression, plays an important regulatory role in MCL-1 overexpression that could promote tumor cell survival by inhibiting apoptosis. Enforced miR-29a expression was found to modulate apoptosis through inhibition of MCL-1 expression in ALCL cell lines and in a xenografted model, with a concomitant tumor growth reduction. Thus, synthetic miR-29a represents a potential new tool to affect tumorigenesis in these lymphomas.