Sphingosine Kinase 1 is associated with the Activation, Proliferation and Survival of Chronic Lymphocytic Leukemia Cells

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

Nueva York

Workshop; International Workshop on Chronic Lymphocytic Leukemia (XVII iwCLL 2017); 2017

Leukemic cells from CLL patients can survive and proliferate within lymphoid tissues where the supportive microenvironment favors their accumulation. We have previously reported that the activation of CLL cells reduces the expression of the main receptor for sphingosine 1-phosphate (S1P) (Borge M, J Immunol, 2014), a bioactive phospholipid that participates in lymphocyte egress from lymphoid tissues. S1P, which is generated by sphingosine kinases (SK1 and SK2) and degraded by S1P lyases (S1PL), also favors cell growth and survival through independent intracellular mechanisms. Given that several studies implicated the SK/S1P/S1PL pathway as an essential regulator of cell proliferation and survival in cancer cells, the aim of our study was to evaluate its role in leukemic B cells from CLL patients.We measured the basal expression of SKs and S1PL by qRT-PCR on purified B cells from CLL patients (n=30) and aged-matched healthy donors (n=10), and found that CLL cells express higher levels of SK1 (p