Dynamic Single-Cell Network Profiles in Acute Myelogenous Leukemia Are Associated with Patient Response to Standard Induction Therapy
- 14 July 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 16 (14) , 3721-3733
- https://doi.org/10.1158/1078-0432.ccr-10-0093
Abstract
Purpose: Complete response to induction chemotherapy is observed in ∼60% of patients with newly diagnosed non-M3 acute myelogenous leukemia (AML). However, no methods exist to predict with high accuracy at the individual patient level the response to standard AML induction therapy. Experimental Design: We applied single-cell network profiling (SCNP) using flow cytometry, a tool that allows a comprehensive functional assessment of intracellular signaling pathways in heterogeneous tissues, to two training cohorts of AML samples (n = 34 and 88) to predict the likelihood of response to induction chemotherapy. Results: In the first study, univariate analysis identified multiple signaling “nodes” (readouts of modulated intracellular signaling proteins) that correlated with response (i.e., AUCROC ≥ 0.66; P ≤ 0.05) at a level greater than age. After accounting for age, similar findings were observed in the second study. For patients Conclusions: These data emphasize the value of performing quantitative SCNP under modulated conditions as a basis for the development of tests highly predictive for response to induction chemotherapy. SCNP provides information distinct from other known prognostic factors such as age, secondary AML, cytogenetics, and molecular alterations and is potentially combinable with the latter to improve clinical decision making. Independent validation studies are warranted. Clin Cancer Res; 16(14); 3721–33. ©2010 AACR.Keywords
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