title: Increased expression of protease-activated receptor 1 (PAR-1) in human leukemias.
abstract: 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.
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, RJ, Brazil.
authors.forename: Camilla de S B
authors.initials: Cde S
authors.lastname: Veiga
authors.forename: Tatiana C
authors.initials: TC
authors.lastname: Carneiro-Lobo
authors.forename: Cláudia J B P
authors.initials: CJ
authors.lastname: Coelho
authors.forename: Silvia M F
authors.initials: SM
authors.lastname: Carvalho
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Maia
authors.forename: Flávia C
authors.initials: FC
authors.lastname: Vasconcelos
authors.forename: Eliana
authors.initials: E
authors.lastname: Abdelhay
authors.forename: André L
authors.initials: AL
authors.lastname: Mencalha
authors.forename: Aline F
authors.initials: AF
authors.lastname: Ferreira
authors.forename: Fabíola A
authors.initials: FA
authors.lastname: Castro
authors.forename: Robson Q
authors.initials: RQ
authors.lastname: Monteiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000503:physiopathology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000503:physiopathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000503:physiopathology; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000503:physiopathology; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D044463:Receptor, PAR-1