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Pregled bibliografske jedinice broj: 793930

NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation

Pozzo, F.; Bittolo, T.; Arruga, F.; Bulian, P.; Macor, P.; Tissino, E.; Gizdić, Branimir; Rossi, F.M.; Bomben, R.; Zucchetto, A. et al.
NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation // Leukemia, 30 (2016), 182-189 doi:10.1038/leu.2015.182 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 793930 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation

Autori
Pozzo, F. ; Bittolo, T. ; Arruga, F. ; Bulian, P. ; Macor, P. ; Tissino, E. ; Gizdić, Branimir ; Rossi, F.M. ; Bomben, R. ; Zucchetto, A. ; Benedetti, D. ; Degan, M. ; D'Arena, G. ; Chiarenza, A. ; Zaja, F. ; Pozzato, G. ; Rossi, D. ; Gaidano, G. ; Del Poeta, G. ; Deaglio, S. ; Gattei, V. ; Dal Bo, M.

Izvornik
Leukemia (0887-6924) 30 (2016); 182-189

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
NOTCH1; CD20; B-CLL; RPBJ; HDAC

Sažetak
In chronic lymphocytic leukemia (CLL), NOTCH1 mutations have been associated with clinical resistance to the anti-CD20 rituximab, although the mechanisms behind this peculiar behavior remain to be clarified. In a wide CLL series (n=692), we demonstrated that CLL cells from NOTCH1-mutated cases (87/692) were characterized by lower CD20 expression and lower relative lysis induced by anti-CD20 exposure in vitro. Consistently, CD20 expression by CLL cells was upregulated in vitro by gamma-secretase inhibitors or NOTCH1-specific small interfering RNA and the stable transfection of a mutated (c.7541- 7542delCT) NOTCH1 intracellular domain (NICD-mut) into CLL-like cells resulted in a strong downregulation of both CD20 protein and transcript. By using these NICD-mut transfectants, we investigated protein interactions of RBPJ, a transcription factor acting either as activator or repressor of NOTCH1 pathway when respectively bound to NICD or histone deacetylases (HDACs). Compared with controls, NICD-mut transfectants had RBPJ preferentially complexed to NICD and showed higher levels of HDACs interacting with the promoter of the CD20 gene. Finally, treatment with the HDAC inhibitor valproic acid upregulated CD20 in both NICD-mut transfectants and primary CLL cells. In conclusion, NOTCH1 mutations are associated with low CD20 levels in CLL and are responsible for a dysregulation of HDAC- mediated epigenetic repression of CD20 expression.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti



POVEZANOST RADA

Projekti:
198-1980955-0953 - Imunobiologija kronične B-limfocitne leukemije i mikrookoliš (Jakšić, Ozren, MZOS ) ( CroRIS)

Ustanove:
Klinička bolnica "Dubrava"

Profili:

Avatar Url Branimir Gizdić (autor)

Poveznice na cjeloviti tekst rada:

doi www.nature.com

Citiraj ovu publikaciju:

Pozzo, F.; Bittolo, T.; Arruga, F.; Bulian, P.; Macor, P.; Tissino, E.; Gizdić, Branimir; Rossi, F.M.; Bomben, R.; Zucchetto, A. et al.
NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation // Leukemia, 30 (2016), 182-189 doi:10.1038/leu.2015.182 (međunarodna recenzija, članak, znanstveni)
Pozzo, F., Bittolo, T., Arruga, F., Bulian, P., Macor, P., Tissino, E., Gizdić, B., Rossi, F., Bomben, R. & Zucchetto, A. (2016) NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation. Leukemia, 30, 182-189 doi:10.1038/leu.2015.182.
@article{article, author = {Pozzo, F. and Bittolo, T. and Arruga, F. and Bulian, P. and Macor, P. and Tissino, E. and Gizdi\'{c}, Branimir and Rossi, F.M. and Bomben, R. and Zucchetto, A. and Benedetti, D. and Degan, M. and D'Arena, G. and Chiarenza, A. and Zaja, F. and Pozzato, G. and Rossi, D. and Gaidano, G. and Del Poeta, G. and Deaglio, S. and Gattei, V. and Dal Bo, M.}, year = {2016}, pages = {182-189}, DOI = {10.1038/leu.2015.182}, keywords = {NOTCH1, CD20, B-CLL, RPBJ, HDAC}, journal = {Leukemia}, doi = {10.1038/leu.2015.182}, volume = {30}, issn = {0887-6924}, title = {NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation}, keyword = {NOTCH1, CD20, B-CLL, RPBJ, HDAC} }
@article{article, author = {Pozzo, F. and Bittolo, T. and Arruga, F. and Bulian, P. and Macor, P. and Tissino, E. and Gizdi\'{c}, Branimir and Rossi, F.M. and Bomben, R. and Zucchetto, A. and Benedetti, D. and Degan, M. and D'Arena, G. and Chiarenza, A. and Zaja, F. and Pozzato, G. and Rossi, D. and Gaidano, G. and Del Poeta, G. and Deaglio, S. and Gattei, V. and Dal Bo, M.}, year = {2016}, pages = {182-189}, DOI = {10.1038/leu.2015.182}, keywords = {NOTCH1, CD20, B-CLL, RPBJ, HDAC}, journal = {Leukemia}, doi = {10.1038/leu.2015.182}, volume = {30}, issn = {0887-6924}, title = {NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia : evidence for a NOTCH1 mutation-driven epigenetic dysregulation}, keyword = {NOTCH1, CD20, B-CLL, RPBJ, HDAC} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE

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