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

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Heterogeneous-Nuclear Ribonucleoproteins
Myeloid Cells
Granulocyte Colony-Stimulating Factor
Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Granulocyte Colony-Stimulating Factor Receptors
CCAAT-Enhancer-Binding Proteins
Oncogene Proteins
Protein Biosynthesis
Carrier Proteins
Cell Death
Down-Regulation
Bone Marrow
RNA
Messenger RNA
Ectopic Gene Expression

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Perrotti, D., Cesi, V., Trotta, R., Guerzoni, C., Santilli, G., Campbell, K., ... 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

BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2. / Perrotti, Danilo; Cesi, Vincenzo; Trotta, Rossana; Guerzoni, Clara; Santilli, Giorgia; Campbell, Kenneth; Iervolino, Angela; Condorelli, Fabrizio; Gambacorti-Passerini, Carlo; Caligiuri, Michael A.; Calabretta, Bruno.

In: Nature Genetics, Vol. 30, No. 1, 01.2002, p. 48-58.

Research output: Contribution to journalArticle

Perrotti, D, Cesi, V, Trotta, R, Guerzoni, C, Santilli, G, Campbell, K, Iervolino, A, Condorelli, F, Gambacorti-Passerini, C, Caligiuri, MA & Calabretta, B 2002, 'BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2', Nature Genetics, vol. 30, no. 1, pp. 48-58. https://doi.org/10.1038/ng791
Perrotti D, Cesi V, Trotta R, Guerzoni C, Santilli G, Campbell K et al. BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2. Nature Genetics. 2002 Jan;30(1):48-58. https://doi.org/10.1038/ng791
Perrotti, Danilo ; Cesi, Vincenzo ; Trotta, Rossana ; Guerzoni, Clara ; Santilli, Giorgia ; Campbell, Kenneth ; Iervolino, Angela ; Condorelli, Fabrizio ; Gambacorti-Passerini, Carlo ; Caligiuri, Michael A. ; Calabretta, Bruno. / BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2. In: Nature Genetics. 2002 ; Vol. 30, No. 1. pp. 48-58.
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