In Vitro and In Vivo Expression of the Antimicrobial Peptide LL-37 in CLL

PODAZA, ENRIQUE; YAN, JOY; CROCI, DIEGO; ALMEJÚN, MARÍA BELÉN; PALACIOS, FLORENCIA; RISNIK, DENISE; COLADO, ANA; BORGE, MERCEDES; ELÍAS, ESTEBAN ENRIQUE; FERNÁNDEZ GRECCO, HORACIO; BEZARES, RAIMUNDO FERNANDO; CHIORAZZI, NICHOLAS; GAMBERALE, ROMINA; GIORDANO, MIRTA

New York

Workshop; XVII International Workshop on Chronic Lymphocytic Leukemia; 2017

The maintenance and expansion of CLL B cells depend on signals from themicroenvironment of lymphoid tissues. The crosstalk between malignant cells andtheir milieu is mediated through direct cell contact and soluble factors. LL-37 is aC-terminal peptide proteolytically released from human cathelicidin antimicrobialpeptide (CAMP) by neutrophils, macrophages and epithelial cells uponstimulation. LL-37 has a broad spectrum of antimicrobial and immunomodulatoryactivities, and it was shown to be overexpressed in the tumor microenvironmentof colon and pancreatic cancer patients, where it promotes tumor cell growth (LiD et al, Oncotarget 33:2709, 2014; Sainz B et al, Gut April 3 2015). We havepreviously reported that the exogenous addition of LL-37 to CLL-B cell culturesinhibits spontaneous and drug-induced apoptosis. Here we studied the endogenousexpression of LL-37 in CLL. By comparing gene expression profiles of 25samples from CLL patients and 12 samples from healthy donors, we observed thatLL-37 expression is higher in B cells from CLL patients (P=0.013). Moreover,there was significantly more LL-37 in unmutated IgVH (n=10) than in mutated IgVH CLL samples (n=15) (P=0.005). Then, we activated CLL B cells with antiIgMplus CD40 ligand and evaluated the expression of CAMP mRNA by qRTPCRat 24 h. We found increased levels of CAMP upon activation (control vsactivated B-CLL cells, P