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dc.titleC/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
dc.contributor.authorAlberich-Jordà, M.
dc.contributor.authorWouters, B.
dc.contributor.authorBalastik, M.
dc.contributor.authorShapiro-Koss, C.
dc.contributor.authorZhang, H.
dc.contributor.authorDiRuscio, A.
dc.contributor.authorRadomska, H.S.
dc.contributor.authorEbralidze, A.K.
dc.contributor.authorAmabile, G.
dc.contributor.authorYe, M.
dc.contributor.authorZhang, J.
dc.contributor.authorLowers, I.
dc.contributor.authorAvellino, R.
dc.contributor.authorMelnick, A.
dc.contributor.authorFigueroa, M.E.
dc.contributor.authorValk, P.J.M.
dc.contributor.authorDelwel, R.
dc.contributor.authorTenen, D.G.
dc.identifier.citationAlberich-Jordà, M., Wouters, B., Balastik, M., Shapiro-Koss, C., Zhang, H., DiRuscio, A., Radomska, H.S., Ebralidze, A.K., Amabile, G., Ye, M., Zhang, J., Lowers, I., Avellino, R., Melnick, A., Figueroa, M.E., Valk, P.J.M., Delwel, R., Tenen, D.G. (2012-12-03). C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia. Journal of Clinical Investigation 122 (12) : 4490-4504. ScholarBank@NUS Repository.
dc.description.abstractC/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.
dc.description.sourcetitleJournal of Clinical Investigation
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