Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States;
Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large cell lymphoma(DLBCL), we observed higher levels of JAK/STAT pathway related serum cytokines (IL-6, IL-10, EGF, IL-2) vs controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event free survival (EFS) than patients with low levels (p>0.01) and high IL-10 correlated with high LDH (p=0.0085) and higher International Prognostic Index scores (p=0.01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10R complex upregulated JAK2 signaling. Neutralizing antibody to IL-10 inhibited constitutive as well as IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2 positive DLBCL cells; there was minimal effect on phospho-JAK2 negative cells. Apoptosis induced by JAK2 inhibition was dependent upon inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.
Am old enough to understand the difference between the Bay of Pigs - and roasting a pig at a epicurian feast. Been thru the hippy, yippie and yuppie years - always remaining who I am.
Very much believe in "Sing your own song - weave your own tapestry"
Am young enough to still know the thrill of new discoveries, the beauty of the evening, to celebrate the joy of another tommorow.
Survived these many decades with a severe medical problems. Sorting out the maze of now having two lymphomas and all their nasty little companions, but I continue.
Besides, being a simple iconoclastic eclectic, have been called many things. An incurable romanticist - with a strong touch of reality. Thinker, intellectual (God, how I hate that term) - been told I am a lion with the heart of the poet.
Know how to wage war and conquer my foes - but would rather be known as one who brings hope and life. To bring hope into anothers life is the ultimate of joys.
Life should be about bringing hope, peace, vision... a sense of purpose beyond yourself.