Data from Proteasome Enzymatic Activities in Plasma as Risk Stratification of Patients with Acute Myeloid Leukemia and Advanced-Stage Myelodysplastic Syndrome

Abstract

<div>Abstract<p><b>Purpose:</b> Cytogenetic abnormalities are currently the most important predictors of response and clinical outcome for patients with acute myeloid leukemia (AML) or advanced-stage myelodysplastic syndrome (MDS). Because clinical outcomes vary markedly within cytogenetic subgroups, additional biological markers are needed for risk stratification.</p><p><b>Experimental Design:</b> We assessed the utility of measuring pretreatment proteasome chymotrypsin-like, caspase-like, and trypsin-like activities in plasma to predict response and survival of patients with AML (<i>n</i> = 174) or advanced-stage MDS (<i>n</i> = 52).</p><p><b>Results:</b> All three enzymatic activities were significantly (<i>P</i> < 0.001) increased in the plasma of patients with AML and MDS compared with normal controls. Both chymotrypsin-like and caspase-like activities, but not trypsin-like activity, correlated with outcome. Chymotrypsin-like and caspase-like activities, but not trypsin-like activity, predicted response in univariate analysis (<i>P</i> = 0.002). However, only chymotrypsin-like activity was independent predictor of response from age grouping (<70 versus ≥70 years), cytogenetics, and blood urea nitrogen in multivariate analysis. Similarly, both chymotrypsin-like and caspase-like activities, but not trypsin-like activity, were predictors of overall survival in univariate analysis (<i>P</i> < 0.0001), but only chymotrypsin-like activity was independent of cytogenetics, age, performance status, blood urea nitrogen, and β<sub>2</sub>-microglobulin in multivariate Cox regression models. Chymotrypsin-like activity was also a strong independent predictor of survival in patients with intermediate karyotype (<i>n</i> = 124).</p><p><b>Conclusions:</b> Measuring plasma chymotrypsin-like activity may provide a powerful biomarker for risk stratification in patients with AML and advanced-stage MDS, including those with normal karyotype.</p></div>