C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia

0387490 - ÚMG 2013 RIV US eng J - Článek v odborném periodiku
Alberich-Jorda, M. - Wouters, B. - Balaštík, Martin - Shapiro-Koss, C. - Zhang, H. - DiRuscio, A. - Radomska, H.S. - Ebralidze, A.K. - Amabile, G. - Ye, M. - Zhang, J.Y. - Lowers, I. - Avellino, R. - Melcnick, A. - Figueroa, M.E. - Valk, P.J.M. - Delwel, R. - Tenen, D.G.
C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia.
Journal of Clinical Investigation. Roč. 122, č. 12 (2012), s. 4490-4504. ISSN 0021-9738. E-ISSN 1558-8238
Grant ostatní: NIH(US) CA118316; NIH(US) HL56745
Institucionální podpora: RVO:68378050
Klíčová slova: C/EBP transcription factor * acute myeloid leukemia * differentiation
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 12.812, rok: 2012

C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs.
Trvalý link: http://hdl.handle.net/11104/0218699