Abstract 5310: Integrated functional proteomic profiling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): MDS-like signature is associated with favorable outcome in patients with AML
Authors: Chae Young Kwang , Yoo Suk Young , Coombes Kevin R. , Kornblau Steven M. 
Published: May 2015

Background: One third of MDS cases transforms into AML. MDS and AML are considered one spectrum of myeloid stem cell disease. We have previously reported MDS and AML specific proteomic signatures associated with different survival outcomes. However, there exists no study that integrated both MDS and AML cases to explore common proteomic signatures that harbor prognostic implications.

Methods: We collected bone marrow and peripheral blood CD34+ samples from 116 MDS patients and 511 AML (non-APL) patients newly diagnosed at the MD Anderson Cancer Center from 1998 till 2006. Reverse phase protein array (RPPA) platform was used for functional proteomic profiling on 119 proteins and phospho-proteins for cell-cycle, apoptosis, and several signal transduction pathways known to play a role in hematologic malignancies. Each antibody was validated with Western blotting. We integrated the RPPA data between MDS and AML patients via normalization. Kaplan-Meier method was used for survival analysis performed on 90 MDS patients and 415 AML patients who received treatments.

Results: Among 627 patients with MDS or AML, six distinct functional proteomic signatures were identified; signature 1 (21.0% of total patients), 2 (15.6%), 3 (15.6%), 4 (16.0%), 5 (24.0%), and 6 (7.7%). Most of patients in signature group 6 had MDS compared with patients in other groups (chi-square test p&lt;0.001, proportion of MDS patients in group 1 (7.5%), 2 (0%), 3 (15.2%), 4 (9.9%), 5 (28.9%), and 6 (69.2%); thus, group 1 to 5: AML-like signature vs. group 6: MDS-like signature). Among MDS patients, 10.3% of patients in group 6 later transformed into AML while 1.8% of patients in other groups did so. Among AML patients, 1.0% of patients in group 6 had history of MDS while 4.4% of patients in other groups did so.

Six groups demonstrated differences in complete remission (CR) rate (chi-square test p=0.03). Among patients with MDS or AML who received treatment, CR rate in patients in group 6 was 61.5% while that in patients in other groups was 51.1%. However, six groups did not differ in CR duration. Among MDS patients, there were no statistically significant differences in overall survival between group 6 and other groups (log-rank test p=0.63, HR=0.87). However, among AML patients, patients in group 6 was associated with superior overall survival compared with patients in other groups (log-rank test p=0.02, HR=0.39).

Conclusion: Integrated functional proteomic profiling revealed six common distinct signature groups that are associated with CR rate and overall survival outcome. In AML patients, MDS-like signature (group 6) was linked with favorable survival outcome and possibly higher CR rate.

Citation Format: Young Kwang Chae, Suk Young Yoo, Kevin R. Coombes, Steven M. Kornblau. Integrated functional proteomic profiling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): MDS-like signature is associated with favorable outcome in patients with AML. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5310. doi:10.1158/1538-7445.AM2014-5310