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

Blood Cells Mol Dis. 2011 Mar 15;46(3):230-4. doi: 10.1016/j.bcmd.2010.12.005. Epub 2011 Jan 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • 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
  • Receptor, PAR-1 / genetics
  • Receptor, PAR-1 / metabolism*
  • Young Adult

Substances

  • Receptor, PAR-1