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 Acute myeloid leukemia (AML). Defining the features that allow identification of APL patients likely to relapse after therapy remains challenging.

Experimental design: Proteomic profiling is performed on 20 newly diagnosed APL, 205 non-APL AML, and 10 normal CD34+ samples using Reverse Phase Protein Arrays probed with 230 antibodies.

Results: Comparison between APL and non-APL AML samples identifies 8.3% of the proteins to be differentially expressed. Proteins higher expressed in APL are involved in the pro-apoptotic pathways or are linked to higher proliferation. The "MetaGalaxy" approach that considers proteins in relation to other assayed proteins stratifies the APL patients into two protein signatures. All of the relapse patients (n = 4/4) are in protein signature 2 (S2). Comparison of proteins between the signatures shows significant differences in relative expression for 38 proteins. Protein expression summary plots suggest 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 is required.