Open AccessClinical relevance of proteomic profiling in <i>de novo</i> pediatric acute myeloid leukemia: a Children’s Oncology Group study
Author(s) -
Fieke W. Hoff,
Anneke D. van Dijk,
Yihua Qiu,
Chenyue W. Hu,
Rhonda E. Ries,
Andrew Ligeralde,
Gaye Jenkins,
Robert B. Gerbing,
Alan S. Gamis,
Richard Aplenc,
E. Anders Kolb,
Todd A. Alonzo,
Soheil Meshinchi,
Amina A. Qutub,
Eveline S.J.M. de Bont,
Terzah M. Horton,
Steven M. Kornblau
Publication year - 2022
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2021.279672
Subject(s) - myeloid leukemia , oncology , myeloid , proteomics , medicine , context (archaeology) , leukemia , bortezomib , omics , biomarker , cancer research , bioinformatics , biology , genetics , gene , paleontology , multiple myeloma
Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patient samples and 30 control CD34+ samples, using the reverse phase protein arrays with 296 strictly validated antibodies. The multi-step “MetaGalaxy” analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein expression patterns. PrSIGs were associated with cytogenetics and mutational state, and with both favorable or unfavorable prognosis. Analysis based on treatment (i.e., ADE vs. ADE plus bortezomib (ADEB)) identified three PrSIGs that did better with ADEB vs. ADE. When PrSIGs were studied in the context of genetic subgroups, PrSIGs were independently prognostic after multivariate analysis, suggesting a potential value for proteomics in combination with current classification systems. Proteins with universally increased (n=7) or decreased (n=17) expression were observed across PrSIGs. Expression of certain proteins significantly differentially expressed from normal could be identified, forming a hypothetical platform for personalized medicine.