Cancers, Vol. 16, Pages 1448: Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial

Cancers, Vol. 16, Pages 1448: Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial Cancers doi: 10.3390/cancers16081448 Authors: Anneke D. van Dijk Fieke W. Hoff Yihua Qiu Stefan E. Hubner Robin L. Go Vivian R. Ruvolo Amanda R. Leonti Robert B. Gerbing Alan S. Gamis Richard Aplenc Edward A. Kolb Todd A. Alonzo Soheil Meshinchi Eveline S. J. M. de Bont Terzah M. Horton Steven M. Kornblau 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 ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research