Proteomic Profiling of Acute Promyelocytic Leukemia Identifies Two Protein Signatures Associated with Relapse.

PURPOSE: Acute promyelocytic leukemia (APL) is the most prognostically favorable subtype of AML. Defining the features that allow identification of acute promyelocytic leukemia (APL) patients likely to relapse after therapy remains challenging.

EXPERIMENTAL DESIGN: Proteomic profiling was performed on 20 newly diagnosed APL, 205 non-APL acute myeloid leukemia (AML), and 10 normal CD34+ samples using Reverse Phase Protein Arrays probed with 230 antibodies.

RESULTS: Comparison between APL and non-APL AML samples identified 8.3% of the proteins to be differentially expressed. Proteins higher expressed in APL were involved in the pro-apoptotic pathways or were linked to higher proliferation. The ''MetaGalaxy'' approach that considers proteins in relation to other assayed proteins, stratified the APL patients into two protein signatures. All of the relapse patients (n = 4/4) were in protein signature 2 (S2). Comparison of proteins between the signatures showed significant differences in relative expression for 38 proteins. Protein expression summary plots suggested less translational activity in combination with a less proliferative character for S2 compared to signature 1.

CONCLUSIONS AND CLINICAL RELEVANCE: This study provides a potential proteomic-based classification of APL patients that may be useful for risk stratification and therapeutic guidance. Validation in a larger independent cohort in required. This article is protected by copyright. All rights reserved.