Increased expression of protease-activated receptor 1 (PAR-1) in human leukemias

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2011-03, Vol.46 (3), p.230-234
• Main Authors: Veiga, Camilla de S.B., Carneiro-Lobo, Tatiana C., Coelho, Cláudia J.B.P., Carvalho, Silvia M.F., Maia, Raquel C., Vasconcelos, Flávia C., Abdelhay, Eliana, Mencalha, André L., Ferreira, Aline F., Castro, Fabíola A., Monteiro, Robson Q.
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chronic myeloid leukemia; Female; Gene Expression Regulation, Leukemic; Humans; Leukemia - physiopathology; Leukemia, Lymphocytic, Chronic, B-Cell - physiopathology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - physiopathology; Leukemia, Myeloid, Acute - physiopathology; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology; Protease-activated receptor 1 (PAR-1); Receptor, PAR-1 - genetics; Receptor, PAR-1 - metabolism; Thrombin; Young Adult
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2010.12.005

Protease-activated receptor 1 (PAR-1) is a G-protein-coupled receptor that is overexpressed in solid tumors, being associated with several pro-tumoral responses including primary growth, invasion, metastasis and angiogenesis. Expression of PAR-1 in human leukemic cell lines is reported but the status of its expression in human leukemic patients is currently unknown. In this study we evaluated the expression pattern of PAR-1 in patients with the four main types of leukemia – chronic lymphocytic leukemia subtype B (B-CLL), acute lymphoblastic leukemia subtype B (B-ALL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Flow cytometry analyses show that lymphocytes from B-CLL patients express this receptor at similar levels to healthy individuals. On the other hand, it was observed a significant increase in PAR-1 expression in B-ALL lymphocytes as compared to B-CLL and healthy donors. Flow cytometric and real-time PCR demonstrated a significant increase in PAR-1 expression in granulocytes from CML patients in blast phase (CML-BP) but not in chronic phase (CML-CP) as compared to healthy donors. Finally, a significant increase in PAR-1 expression has been also observed in blasts from AML (subtypes M4 and M5) patients, as compared to monocytes or granulocytes from healthy donors. We conclude that PAR-1 might play an important biological role in aggressive leukemias and might offer additional strategies for the development of new therapies.