Volumen: 14 # Number : 1
Publication Date : Enero - Marzo Year: 2010
Authors: Carlos D. Chazarreta, Nora P. Goette, Paola R. Lev, Juan P. Salim, Felisa C. Molinas, Rosana F. Marta
Abstract: IL-6 acts through its membrane bound and soluble (IL-
6sR) receptors. The latter confers IL-6 sensitivity to cells
that lack the anchored receptor. Previously, we have
reported IL-6sR increase in essential thrombocythemia (ET),
a myeloproliferative neoplasm (MN). In the present work,
we evaluated the effect of IL-6/IL-6sR complex (COMP)
compared to that of IL-6, regarding its ability to protect
CD34+ progenitors form apoptosis and to activate JAK/
STAT in platelets, from both, MN patient and normal
samples. Altogether, progenitors from patients and controls
underwent less apoptosis in the presence of COMP than
with IL-6 (activated caspase 3 p=0.001; anexin V expression p=0.029). JAK2 and STAT3 activation was evaluated by
western-blot comparing the phosphorylated and the total
protein induced by COMP (RelCOMP) and thrombopoietin
(RelTPO) and calculating the ratio (R COMP/TPO).
Patients harbouring JAK2-V617F had increased STAT3 R
COMP/TPO, 2.03 (0.45-3.03) (median, range) than controls,
0.63 (0.014-0.8) and patients without the mutation, 0.75
(0.005-1.12) ANOVA p=0.018. JAK2 activation showed the
same pattern but did not reach statistical significance.
These results suggest that COMP is more effective than
IL-6 in protecting hematopoietic progenitors from
apoptosis. These findings together with the increased IL-
6sR levels previously found in ET, suggest that high IL-6sR
levels could favour megakaryocytic progenitors survival in
MN. This protection would occur through JAK2/STAT3,
being more efficient in patients carrying the JAK2-V617F
mutation.
Key words: Interleukin 6 receptor, Platelets, JAK2-
V617F, Hematopoietic progenitors, Apoptosis.
Pages : 11-17
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