BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2

Danilo Perrotti, Vincenzo Cesi, Rossana Trotta, Clara Guerzoni, Giorgia Santilli, Kenneth Campbell, Angela Iervolino, Fabrizio Condorelli, Carlo Gambacorti-Passerini, Michael A. Caligiuri, Bruno Calabretta

Research output: Contribution to journalArticle

Abstract

The arrest of differentiation is a feature of both chronic myelogenous leukemia cells in myeloid blast crisis and myeloid precursors that ectopically express the p210BCR-ABL oncoprotein; however, its underlying mechanisms remain poorly understood. Here we show that expression of BCR-ABL in myeloid precursor cells leads to transcriptional suppression of the granulocyte colony-stimulating factor receptor G-CSF-R (encoded by CSF3R), possibly through down-modulation of C/EBPα - the principal regulator of granulocytic differentiation. Expression of C/EBPα protein is barely detectable in primary marrow cells taken from individuals affected with chronic myeloid leukemia in blast crisis. In contrast, CEBPA RNA is clearly present. Ectopic expression of C/EBPα induces granulocytic differentiation of myeloid precursor cells expressing BCR-ABL. Expression of C/EBPα is suppressed at the translational level by interaction of the poly(rC)-binding protein hnRNP E2 with CEBPA mRNA, and ectopic expression of hnRNP E2 in myeloid precursor cells down-regulates both C/EBPα and G-CSF-R and leads to rapid cell death on treatment with G-CSF (encoded by CSF3). Our results indicate that BCR-ABL regulates the expression of C/EBPα by inducing hnRNP E2 - which inhibits the translation of CEBPA mRNA.

Original languageEnglish
Pages (from-to)48-58
Number of pages11
JournalNature Genetics
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2002

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    Perrotti, D., Cesi, V., Trotta, R., Guerzoni, C., Santilli, G., Campbell, K., Iervolino, A., Condorelli, F., Gambacorti-Passerini, C., Caligiuri, M. A., & Calabretta, B. (2002). BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2. Nature Genetics, 30(1), 48-58. https://doi.org/10.1038/ng791