Publication Date:
2011-11-18
Description:
Abstract 938 Pediatric acute myeloid leukemia (AML) remains a devastating disease with a relapse rate near 50%. Kinase inhibitors are being incorporated into treatments, yet the signaling abnormalities targeted by these drugs remain poorly understood. Pathways involving Stat3 and Stat5 are known to be aberrantly active in AML, and increased activity has been associated with chemoresistant disease and poor outcome. Our hypothesis is that analysis of Stat3/5 activation patterns will delineate signaling abnormalities, and thereby guide the development of targeted therapies. We performed FACS analysis of the Stat3/5 signaling pathways in 140 diagnostic bone marrow samples from patients on the AML study CCG 2961. After thawing, cells were rested in serum-free medium for 2 hr. We measured tyrosine-phosphorylated Stat3 (pY-Stat3), serine-phosphorylated Stat3 (pS-Stat3) and pY-Stat5 in unstimulated cells, cells stimulated with low (1 ng/ml), intermediate (10 ng/ml), or high (100 ng/ml) dose G-CSF, and cells stimulated with low (0.5 + 1), intermediate (5 + 10), or high (50 + 100) dose IL-6 + soluble IL-6 receptor alpha. Constitutively phosphorylated proteins were quantified as the percent of events in the positive gate in unstimulated cells. Constitutive pY-Stat3 and pY-Stat5 were found to be common and highly variable. The median percent of pY-Stat3+ events was 37.3% (range 0.1–91.8%); the median %pY-Stat5+ was 18.6% (range 0.5–86.5%). In contrast, pS-Stat3 was generally low (median 3.63%, range 0.1–78.2%). There was non-significant correlation between %pY-Stat3+ and %pY-Stat5+. There was a significant correlation between %pY-Stat3+ and %total Stat3+, with Pearson correlation coefficient R=0.523 (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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