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october 7-9, 2012 • NEW ORLEANS, LA
in Complex Systems Sciences, Mahidol University,
5
Department of Medicine, Faculty of Medicine Siriraj
Hospital, Mahidol University
Thalassemias are inherited hemoglobinopathies
characterized by absent or partial production of α- or
β-globin chain synthesis. Several thalassemia genotypes
exist, and the corresponding manifestations can vary
from barely detectable abnormalities to severe even fatal
anemia. Profound hemostatic changes with thromboembolic
complications are common in thalassemia patients. Several
etiologic factors including oxidative damage of red blood
cells (RBCs), platelet activation and the high level of
membrane-derived microparticles (MPs) stemming from
blood cells are thought to be responsible for the associated
thrombotic risk, but the mechanisms remain unclear.
In this communication, we report the oxidative stress,
procoagulant properties and proteomic profiles as well as
their number and cellular origin of these MPs isolated from
β-thalassemia/Hemoglobin E patients’ blood. Flow cytometric
results showed that platelet-free-plasma (PFP) MPs from
thalassemia patients expressed significantly higher levels
of phosphatidylserine (PS)-bearing MPs than those from
normal subjects. The high levels of these PS-bearing
MPs correlated with increased platelet counts and their
procoagulant activity. These PS-bearing MPs showed mostly
platelet and RBC origin which both had high levels of oxidant
activity. Proteome and Western blot analyses of isolated
PFP MPs from thalassemia displayed several distinct
protein features that involved in regulation of cell stress, i.e.
peroxiredoxin 6, apolipoprotein E, heat-shock protein 90, etc.
These findings suggest that elevated oxidative damage in
platelets and RBCs potentially induce MP formation, and that
these MPs contain proteins with oxidative features that might
aggravate thrombotic events when the number is excessive
as commonly seen in thalassemia patients.
P31
DFTD AN INFECTIOUS PARASITIC CANCER
Terry Pinfold, Greg Woods, Alexandre Kriess, Gabriella
Brown
Menzies Research Institute Tasmania
Devil Facial Tumor Disease (DFTD) is a truly infectious
cancer. It is not caused by a viral or bacterial infection or
carcinogens in the environment. It is a parasitic clonal cell
line transmitted between hosts through the natural biting
behaviour of Tasmanian devils. The disease appears limited
to Tasmanian devils which is a unique species of carnivorous
marsupial endemic to the island state of Tasmania, just south
of mainland Australia. It is highly infectious, has a 100%
mortality rate, and has decimated the population to less than
20% of previous estimates. This single disease is expected
to cause the extinction of the Tasmanian devil in the wild
within the next 30 years. We have developed a mouse
model to study DFTD and trial immunotherapy and vaccine
treatments. Current work includes “devilising” the NOD/SCID
mice by partial reconstitution of their immune system with
effector cells from Tasmanian devils. Flow cytometry has
been used to identify antibodies against surface antigens
of viable DFTD cells and quantify cytokine responses to
DFTD. However, the optimization of a non-radioactive
cytotoxicity assay for DFTD proved challenging. For the first
time we have been able to successfully induce protective
cytotoxic responses with the Tasmanian devil effector cells.
We are exploiting a sensitive flow cytometry based assay
to measure the cytotoxic responses being induced by
Tasmanian devils lymphocytes. We are optimistic of a future
immunotherapy against DFTD. Funding: Australian Research
Council Grants and Dr Eric Guiler Tasmanian Devil Research
Grants
POSTER ABSTRACTS