Document Type
Article
Publication Date
4-9-2024
Identifier
DOI: 10.3390/cancers16081448; PMCID: PMC11048007
Abstract
The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and higher 3-year relapse risk after AML standard treatment compared to low expressions (52% vs. 29%, p = 0.005). The high-HME profile correlated with more transposase-accessible chromatin, as demonstrated via ATAC-sequencing, and the bortezomib addition improved the 3-year overall survival compared with standard therapy (62% vs. 75%, p = 0.033). These data suggest that there are pediatric AML populations that respond well to bortezomib-containing chemotherapy.
Journal Title
Cancers (Basel)
Volume
16
Issue
8
Keywords
bortezomib; pediatric acute myeloid leukemia; reverse-phase protein array
Recommended Citation
van Dijk AD, Hoff FW, Qiu Y, et al. Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial. Cancers (Basel). 2024;16(8):1448. Published 2024 Apr 9. doi:10.3390/cancers16081448
Comments
Grants and funding
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Publisher's Link: https://www.mdpi.com/2072-6694/16/8/1448