NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: link between the NOTCH1 and the NF-κB pathways
- Benedetti, D
- Tissino, E
- Pozzo, F
- Bittolo, T
- Caldana, C
- Perini, C
- Martorelli, D
- Bravin, V
- D'Agaro, T
- Rossi, F M
- Bomben, R
- Santinelli, E
- Zaja, F
- Pozzato, G
- Chiarenza, A
- Di Raimondo, F
- Del Poeta, G
- Rossi, D
- Gaidano, G
- Dal Bo, M
- Gattei, V
- Zucchetto, A
DOIAbstract
In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the very-late-activation-4 integrin, a well-known key regulator of microenviromental interactions, and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0.0001), occurring also outside the trisomy 12 CLL subset. Using both the MEC-1 CLL-like cells stably transfec...