Sphingosine kinase 1 participates in the activation, proliferation and survival of chronic lymphocytic leukemia cells

ALMEJÚN, MARÍA BELÉN; BORGE, MERCEDES; COLADO, ANA; ELÍAS, ESTEBAN ENRIQUE; PODAZA, ENRIQUE; RISNIK, DENISE; DE BRASI, CARLOS DANIEL; STANGANELLI, CARMEN; SLAVUTSKY, IRMA; CABREJO, MARÍA; FERNÁNDEZ-GRECCO, HORACIO; BEZARES, RAIMUNDO FERNANDO; CRANCO, SANTIAGO; BURGOS, RUBÉN ÁNGEL; SÁNCHEZ-ÁVALOS, JULIO CÉSAR; OPPEZZO, PABLO; GIORDANO, MIRTA; GAMBERALE, ROMINA

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Año: 2017 vol. 102 p. 257 - 260

0390-6078

Sphingosine kinases (SKs) have received the most attention as important enzymes in cancer biology. They participate in the regulation of bioactive sphingolipid metabolism by producing sphingosine-1 phosphate (S1P) which mediates several biological functions, including cell growth, differentiation, cell survival, migration, and angiogenesis among other tasks. Taken together, the results presented herein and our previous data showing that the activation of CLL cells transiently impair the expression of S1PR1, allow us to hypothesize about the role of the SK1/S1P/S1PL axis in CLL. Thus, the possibility exists that microenvironment signals from lymphoid tissues, by increasing SK1/S1PL ratios in leukemic CLL cells, favors S1P production. Exported S1P can then bind S1PRs, reduce S1PR1 expression6 and transduce stimulating signals to the leukemic clone.In conclusion, our results suggest that the SK/S1P/S1PL pathway supports the survival and proliferation of CLL cells, hence favoring the progression of the disease, thus we encourage the use of SKs inhibitors in combined therapy as a promising treatment option in the future.