Deregulated expression of A1, Bcl-2, Bcl-x(L), and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients

Author(s):Show less -

Lino Gasparotto, Elainy Patricia ^[1] ; Tognon, Raquel ^[1] ; Ferreira, Aline Fernanda ^[1] ; Vilela Oliveira, Gislane Lelis ^[1] ; Bonini Palma, Patricia Vianna ^[2] ; Zanichelli, Maria Aparecida ^[3] ; Souto, Elizabeth Xisto ^[3] ; Engel Velano, Carlos Eduardo ^[4] ; Simoes, Belinda Pinto ^[4] ; Viu Carrara, Rita de Cassia ^[2] ; Kashima, Simone ^[2] ; Covas, Dimas Tadeu ^{[2, 4]} ; de Castro, Fabiola Attie ^[1] ; de Souza, Ana Maria ^[1]

Affiliation

^[1] USP, Dept Clin Anal Toxicol & Food Sci, Fac Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] USP, Hemotherapy Ctr Ribeirao Preto, Sch Med Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Brigadeiro Hosp, Sao Paulo - Brazil

^[4] USP, Dept Clin Med, Fac Med Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Brazilian Journal of Pharmaceutical Sciences; v. 47, n. 4, p. 873-886, OCT-DEC 2011.
• Web of Science Citations: 6

Abstract

Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV). This study evaluated Bcl-2 molecule expression in CD34(+) cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005). CD34(+) cells from PV patients presented higher levels of A1 and Mc1-1 expression (median: 22.6 and 5.2, respectively) in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020); while Bcl-2 and Bcl-x(L) expression decreased in PV patients (0.18 and 1.19) compared with controls (1.39 and 2.01, p=0.006 and p=0.020). CD34(+) cells in PV patients showed an elevated Bid expression (14.4) in comparison with healthy subjects (1.0; p=0.002). Patients' leukocytes showed an A1 augmentation (7.41, p=0.001) and a reduced expression of Bar (0.19; p=0.040) and Bad (0.2; p=0.030). There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis. (AU)