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

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.

HIV genotypes and primary drug resistance among HIV-seropositive blood donors in Brazil: role of infected blood donors as sentinel populations for molecular surveillance of HIV.

BACKGROUND: There are few surveillance studies analyzing genotypes or primary (transmitted) drug resistance in HIV-infected blood donors in Brazil. The aim of this study was to characterize patterns of HIV genotypes and primary resistance among HIV-seropositive donors identified at 4 geographically dispersed blood centers in Brazil. METHODS: All HIV-infected donors who returned for counseling at the 4 REDS-II Hemocenters in Brazil from January 2007 to March 2011 were invited to participate in a case-control study involving a questionnaire on risk factors. Viral sequencing was also offered to positive cases to assign genotypes and to detect and characterize primary resistance to reverse transcriptase and protease inhibitors according to World Health Organization guidelines. RESULTS: Of the 341 HIV-seropositive donors who consented to participate in the risk factor and genetics study, pol sequences were obtained for 331 (97%). Clade B was predominant (76%) followed by F (15%) and C (5%). Primary resistance was present in 36 [12.2%, 95% confidence interval (CI) 8.2 to 15.5] of the 303 individuals not exposed to antiretroviral therapy, varying from 8.2% (95% CI: 2.7 to 13.6) in Recife to 19.4% in São Paulo (95% CI: 9.5 to 29.2); there were no significant correlations with other demographics or risk factors. CONCLUSIONS: Although subtype B remains the most prevalent genotype in all 4 areas, increasing rates of subtype C in Sao Paulo and F in Recife were documented relative to earlier reports. Transmitted drug resistance was relatively frequent, particularly in the city of Sao Paulo which showed an increase compared with previous HIV-seropositive donor data from 10 years ago.