Expression and function of cathelicidin hCAP18/LL-37 in chronic lymphocytic leukemia

PALACIOS, FLORENCIA; YAN, XIAO J; ELÍAS, ESTEBAN E; BEZARES, RAIMUNDO; GAMBERALE, ROMINA; CROCI, DIEGO O; ALMEJÚN, MARÍA BELÉN; BORGE, MERCEDES; FERNÁNDEZ-GRECCO, HORACIO; CHIORAZZI, NICHOLAS; PODAZA, ENRIQUE; RISNIK, DENISE; COLADO, ANA; MORANDE, PABLO E; RABINOVICH, GABRIEL A; GIORDANO, MIRTA

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Lugar: Pavia, Italia; Año: 2020 p. 465 - 469

0390-6078

Here we show that, unlike normal B lymphocytes, leukemic B cells from CLL patientsexpress hCAP18 mRNA and that this expression associates with poor prognosis anddisease stage. Interestingly, we found that circulating CLL cells can produce and releasehCAP18/LL-37 protein upon in vitro activation with microenvironmental stimuli and thisobservation was supported by bone marrow immunohistochemistry. In vitro, exogenousLL-37 delays CLL cell apoptosis, both spontaneous and that induced by chemotherapeuticagents. As an antimicrobial peptide, the main function of LL-37 is to induce bacterial lysisvia the formation of transmembrane pores 15. Cellular membranes associated withcholesterol, such as those from human cells, are resistant to LL-37 toxicity unlesssupraphysiological concentrations are used. By contrast, LL-37 has antiapoptotic effects ina variety of cells including neutrophils through FPRL1 and P2X7 10. We have shown thatthese two receptors are not involved in CLL cell protection by LL-37, but rather thisdepends on CXCR4, a key receptor for CLL cell survival and traffic. Of note, LL-37 wasable to enhance leukemic cell migration towards suboptimal concentrations of CXCL12.In conclusion, our results suggest that hCAP18/LL-37 may have an active role in theCLL-tumor microenvironment by increasing leukemic clone retention and survival inlymphoid tissues.