EXPRESSION OF STEROIDOGENIC ENZYMES IN PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA.

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

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Chronic lymphocytic leukemia (CLL) is a malignant neoplasm that occurs in elderly individuals. It is characterized by proliferation of immunologically immature lymphocytes, which accumulate in blood, bone marrow and lymphatic tissues. Given that this disease displays a gender difference towards the male sex, several authors have studied the possible underlying mechanisms in which sex hormones mediate their effects in lymphocytes. The presence of androgen and estrogen receptors is well established both in healthy individuals and patients with CLL, yet little is known about endogenous synthesis of sex steroids. Previously we have demonstrated the presence of several enzymes required for steroid synthesis in PBMC of healthy individuals. Our goal was to analyze the expression of those enzymes in PBMC from patients with CLL (n=16), and to compare them with that of normal 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. We designed primers for aromatase (Aro), 5α-reductase (5aR) 1 and 3, 3β hydroxysteroid dehydrogenase (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 and 3αHSD1 in patients with CLL, as it occurred in controls. Regarding P450scc, P450c17, 5αR2 and 17βHSD3, the expression showed no difference with healthy subjects. On the other hand, we found decreased expression of 5αR1, 5αR3, 3βHSD, 3αHSD3, 17βHSD1 and 17βHSD5 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 PBMCs from patients with LLC have diminished expression of several enzymes required for sex steroid synthesis, which could compromise their normal functions.