Expression of Steroidogenic Enzymes in Peripheral Blood Mononuclear Cells (PBMC) of Patients with Chronic Lymphocytic Leukemia

GAYDOU L; ROSSETTI MF; CARDOZO MA; BOSQUIAZZO VL; RAMOS JG

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), SAIC.SAI.SAFIS 2018; 2018

SAIC

hronic lymphocytic leukemia (CLL) is a malignant neoplasm that occurs in elderlyindividuals. It is characterized by proliferation of immunologically immature lymphocytes,which accumulate in blood, bone marrow and lymphatic tissues. Given that this diseasedisplays a gender difference towards the male sex, several authors have studied thepossible underlying mechanisms in which sex hormones mediate their effects inlymphocytes. The presence of androgen and estrogen receptors is well established both inhealthy individuals and patients with CLL, yet little is known about endogenous synthesis ofsex steroids. Previously we have demonstrated the presence of several enzymes requiredfor steroid synthesis in PBMC of healthy individuals. Our goal was to analyze the expressionof those enzymes in PBMC from patients with CLL (n=16), and to compare them with that ofnormal subjects (n=17). We separated PBMC from males age 45 to 90 using Ficoll gradient.RNA was obtained with Trizol reagent, and reverse transcribed to obtain cDNA. Wedesigned primers for aromatase (Aro), 5α-reductase (5aR) 1 and 3, 3β hydroxysteroiddehydrogenase (3bHSD), 3α hydroxysteroid dehydrogenase (3aHSD) 1 and 3, P450 side-chain-cleavage (P450scc), cytochrome P450c17, and 17 hydroxysteroid dehydrogenase(17bHSD) 1, 3 and 5. Real-Time PCR was performed using L19 as a housekeeping gene.Statistical analysis were carried out using R software. We found no expression of Aro and3αHSD1 in patients with CLL, as it occurred in controls. Regarding P450scc, P450c17, 5αR2and 17βHSD3, the expression showed no difference with healthy subjects. On the otherhand, we found decreased expression of 5αR1, 5αR3, 3βHSD, 3αHSD3, 17βHSD1 and17βHSD5 in patients with LLC when compared to healthy individuals (p=0,0002; p=0,0011;p=0,0361; p=0,0014; p=0,0070; p=0,0019, respectively). These findings show that PBMCsfrom patients with LLC have diminished expression of several enzymes required for sexsteroid synthesis, which could compromise their normal functions.