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: 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. Kor Tags: Article Source Type: research
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