title: Prognostic role of translocator protein and oxidative stress markers in chronic lymphocytic leukemia patients treated with bendamustine plus rituximab.
abstract: Principally located in the outer mitochondrial membrane, the translocator protein (TSPO) is an 18-kDa transmembrane protein that is a key component of the mitochondrial permeability transition pore. TSPO is associated with a number of biological processes, including apoptosis, the regulation of cellular proliferation, porphyrin transport and heme biosynthesis, immunomodulation, anion transport and the regulation of steroidogenesis. Thus, numerous studies have proposed TSPO as a promising target for novel therapeutic agents, particularly for the treatment of cancer. In the present study, the response of 30 consecutive chronic lymphocytic leukemia (CLL) patients to bendamustine and rituximab treatment was evaluated according to TSPO expression levels. Furthermore, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels, as well as caspase-3 activity were determined. Compared with the lymphocytes of healthy donors, the 30 consecutive CLL patients exhibited increased TSPO expression levels, decreased TBARS and NO levels and reduced caspase-3 activity. Six months after the treatment commenced, the TSPO/mitochondria ratio resembled that of the healthy controls in 24/30 CLL patients. In addition, an increase in TBARS and NO levels, two markers of oxidative stress, and a potentiation of caspase-3 activity in all responder patients was observed. Notably, the six patients who appeared to be resistant to treatment also displayed higher TSPO levels, and lower caspase-3 activity and TBARS levels. These data indicate that TSPO expression may be a molecular prognostic factor in CLL patients.
authors: Local Sanitary Agency, Naples 3 Southern, Torre del Grecco, Naples I-80059, Italy.
authors: Aniello
authors: A
authors: DE Rosa
authors: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples I-80138, Italy.
authors: Silvia
authors: S
authors: Zappavigna
authors: Hematology Unit, San Gennaro Hospital, Naples I-80131, Italy.
authors: Maria Rosaria
authors: MR
authors: Villa
authors: Hematology Unit, San Gennaro Hospital, Naples I-80131, Italy.
authors: Salvatore
authors: S
authors: Improta
authors: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples I-80138, Italy.
authors: Elena
authors: E
authors: Cesario
authors: Hematology Unit, San Gennaro Hospital, Naples I-80131, Italy.
authors: Lucia
authors: L
authors: Mastrullo
authors: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples I-80138, Italy.
authors: Michele
authors: M
authors: Caraglia
authors: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples I-80138, Italy.
authors: Paola
authors: P
authors: Stiuso
keywords: NO; TBARS; apoptosis; chronic lymphocytic leukemia; prognostic factor; translocator protein