The arrest of differentiation is a feature of both chronic myelogenous leukemia cells in myeloid blast crisis and myeloid precursors that ectopically express the p210(BCR-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/EBPalpha-the principal regulator of granulocytic differentiation. Expression of C/EBPalpha 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/EBPalpha induces granulocytic differentiation of myeloid precursor cells expressing BCR-ABL. Expression of C/EBPalpha 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/EBPalpha. 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/EBPalpha by inducing hnRNP E2-which inhibits the translation of CEBPA mRNA.

BCR-ABL suppresses C/EBP alpha expression through inhibitory action of hnRNP E2 / Perrotti, D; Cesi, V; Trotta, R; Guerzoni, Clara; Santilli, G; Campbell, K; Iervolino, A; Condorelli, F; Gambacorti Passerini, C; Caligiuri, Ma; Calabretta, Bruno. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 30:(2002), pp. 48-58. [10.1038/ng791]

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

GUERZONI, Clara;CALABRETTA, Bruno
2002

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 p210(BCR-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/EBPalpha-the principal regulator of granulocytic differentiation. Expression of C/EBPalpha 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/EBPalpha induces granulocytic differentiation of myeloid precursor cells expressing BCR-ABL. Expression of C/EBPalpha 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/EBPalpha. 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/EBPalpha by inducing hnRNP E2-which inhibits the translation of CEBPA mRNA.
2002
30
48
58
BCR-ABL suppresses C/EBP alpha expression through inhibitory action of hnRNP E2 / Perrotti, D; Cesi, V; Trotta, R; Guerzoni, Clara; Santilli, G; Campbell, K; Iervolino, A; Condorelli, F; Gambacorti Passerini, C; Caligiuri, Ma; Calabretta, Bruno. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 30:(2002), pp. 48-58. [10.1038/ng791]
Perrotti, D; Cesi, V; Trotta, R; Guerzoni, Clara; Santilli, G; Campbell, K; Iervolino, A; Condorelli, F; Gambacorti Passerini, C; Caligiuri, Ma; Calabretta, Bruno
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/6166
Citazioni
  • ???jsp.display-item.citation.pmc??? 108
  • Scopus 273
  • ???jsp.display-item.citation.isi??? 252
social impact