TY - JOUR
T1 - Proteasome enzymatic activities in plasma as risk stratification of patients with acute myeloid leukemia and advanced-stage myelodysplastic syndrome
AU - Ma, Wanlong
AU - Kantarjian, Hagop
AU - Bekele, Benjamin
AU - Donahue, Amber C.
AU - Zhang, Xi
AU - Zhang, Zhong J.
AU - O'Brien, Susan
AU - Estey, Elihu
AU - Estrov, Zeev
AU - Cortes, Jorge
AU - Keating, Michael
AU - Giles, Francis
AU - Albitar, Maher
PY - 2009/6/1
Y1 - 2009/6/1
N2 - Purpose: 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. Experimental Design: 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 (n = 174) or advanced-stage MDS (n = 52). Results: All three enzymatic activities were significantly (P < 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 (P = 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 (P < 0.0001), but only chymotrypsin-like activity was independent of cytogenetics, age, performance status, blood urea nitrogen, and β2-microglobulin in multivariate Cox regression models. Chymotrypsinlike activity was also a strong independent predictor of survival in patients with intermediate karyotype (n = 124). Conclusions: 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.
AB - Purpose: 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. Experimental Design: 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 (n = 174) or advanced-stage MDS (n = 52). Results: All three enzymatic activities were significantly (P < 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 (P = 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 (P < 0.0001), but only chymotrypsin-like activity was independent of cytogenetics, age, performance status, blood urea nitrogen, and β2-microglobulin in multivariate Cox regression models. Chymotrypsinlike activity was also a strong independent predictor of survival in patients with intermediate karyotype (n = 124). Conclusions: 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.
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U2 - 10.1158/1078-0432.CCR-08-3034
DO - 10.1158/1078-0432.CCR-08-3034
M3 - Article
C2 - 19458051
AN - SCOPUS:66649101365
SN - 1078-0432
VL - 15
SP - 3820
EP - 3826
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -