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

作者：Lino Gasparotto Elainy Patricia; Tognon Raquel; Ferreira Aline Fernanda; Vilela Oliveira Gislane Lelis; Bonini Palma Patricia Vianna; Zanichelli Maria Aparecida; Souto Elizabeth Xisto; Engel Velano Carlos Eduardo; Simoes Belinda Pinto; Viu Carrara Rita de Cassia; Kashima Simone; Covas Dimas Tadeu; de Castro Fabiola Attie; de Souza Ana Maria^*

来源：Brazilian Journal of Pharmaceutical Sciences, 2011, 47(4): 873-886.

• Polycythemia vera
• Gene mutation
• Gene expression
• Apoptosis
• Bcl-2 family members

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.

• 出版日期2011-12