SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation

Federico Pozzo, Tamara Bittolo, Erika Tissino, Filippo Vit, Elena Vendramini, Luca Laurenti, Giovanni D’Arena, Jacopo Olivieri, Gabriele Pozzato, Francesco Zaja, Annalisa Chiarenza, Francesco Di Raimondo, Antonella Zucchetto, Riccardo Bomben, Francesca Maria Rossi, Federica Maria Rossi, Giovanni Del Poeta, Michele Dal Bo, Valter Gattei

Risultato della ricerca: Contributo in rivistaArticolo in rivista


Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1. Activation of the NOTCH1 signaling and down-regulation of surface CD20 in SF3B1-mutated CLL cells correlate with over-expression of an alternatively spliced form of DVL2, a component of the Wnt pathway and negative regulator of the NOTCH1 pathway. These findings are confirmed by separately analyzing the CD20-dim and CD20-bright cell fractions from SF3B1-mutated cases as well as by DVL2 knock-out experiments in CLL-like cell models. Altogether, the clinical and biological features that characterize NOTCH1-mutated CLL may also be recapitulated in SF3B1-mutated CLL, contributing to explain the poor prognosis of this CLL subset and providing the rationale for expanding novel agents-based therapies to SF3B1-mutated CLL.
Lingua originaleEnglish
pagine (da-a)0-0
Numero di pagine1
Stato di pubblicazionePubblicato - 2020


  • Antigens, CD20
  • Down-Regulation
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Mutation
  • Phosphoproteins
  • Prognosis
  • RNA Splicing Factors
  • Receptor, Notch1


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