Coordinated Dysregulation of Cellular Receptors, Proangiogenic Factors and Intracellular Pathways in Acute leukemia

摘要

To analyse if altered signals are coordinated into the same leukemia, and evaluate their effect on the behaviour of this disease, we have investigated the expression and activation status of the procoagulant/ proangiogenic receptor TF, the angiogenic protein VEGF, and two intracellular proteins involved in their regulation: extracellular regulated kinase (ERK1/2) and nuclear factor kappa-B (NFkB) in bone marrow samples from 20 acute leukemia patients and 10 healthy donors. We found significantly higher mRNA and protein VEGF and TF levels in 17 of 20 samples compared to controls, with a significant positive correlation (p=0.0045). Blast samples showing increased TF and VEGF levels also exhibited enhanced ERK phosphorylation. Increased expression of both TF and VEGF was accompanied by NFkB activation in the same leukemia sample. Clinical studies demonstrated a higher incidence of coagulopathy, recurrence and fatal outcome among patients in which a coordinated increase in the expression and activation of the above mentioned proteins was observed. Our study establishes a coordinated dysregulation of cellular receptors, proangiogenic factors and intracellular pathways into the same leukemia type, which seems to determine a correlation with clinical features.