Increased SYK activity is associated with unfavorable outcome among patients with acute myeloid leukemia

Oncotarget
Katalin BorosScott J Rodig

Abstract

Recent discoveries have led to the testing of novel targeted therapies for the treatment of acute myeloid leukemia (AML). To better inform the results of clinical trials, there is a need to identify and systematically assess biomarkers of response and pharmacodynamic markers of successful target engagement. Spleen tyrosine kinase (SYK) is a candidate therapeutic target in AML. Small-molecule inhibitors of SYK induce AML differentiation and impair leukemia progression in preclinical studies. However, tools to predict response to SYK inhibition and to routinely evaluate SYK activation in primary patient samples have been lacking. In this study we quantified phosphorylated SYK (P-SYK) in AML cell lines and establish that increasing levels of baseline P-SYK are correlated with an increasing sensitivity to small-molecule inhibitors targeting SYK. In addition, we found that pharmacological inhibition of SYK activity extinguishes P-SYK expression as detected by an immunohistochemical (IHC) test. Quantitative analysis of P-SYK expression by the IHC test in a series of 70 primary bone marrow biopsy specimens revealed a spectrum of P-SYK expression across AML cases and that high P-SYK expression is associated with unfavourable outcome in...Continue Reading

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Citations

Dec 11, 2019·International Journal of Molecular Sciences·Valentina SerafinBenedetta Accordi
Apr 4, 2018·Expert Opinion on Investigational Drugs·Sushma Bartaula-BrevikØystein Bruserud
Jul 25, 2019·International Journal of Molecular Sciences·Solène FernandezPierre-Yves Dumas
Nov 8, 2020·Cell Death & Disease·Anna PolakPrzemyslaw Juszczynski
Nov 28, 2019·Cancer Discovery·Anjali CremerKimberly Stegmaier
Aug 11, 2018·Cancer Discovery·Sean D ReiffJennifer A Woyach

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Methods Mentioned

BETA
flow cytometry
biopsies
FACS
surgical resection
electrophoresis
biopsy

Software Mentioned

ImageScope
CorelDRAWX3
R
NISElements D
MedCalc
Aperio Image Analysis
Aperio

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