Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children's Oncology Group study.

TitleClinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children's Oncology Group study.
Publication TypeJournal Article
Year of Publication2022
AuthorsHoff FW, van Dijk AD, Qiu Y, Hu CW, Ries RE, Ligeralde A, Jenkins GN, Gerbing RB, Gamis AS, Aplenc R, E Kolb A, Alonzo TA, Meshinchi S, Qutub AA, De Bont ESJM, Horton TM, Kornblau SM
JournalHaematologica
Date Published2022 Jan 13
ISSN1592-8721
Abstract

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.

DOI10.3324/haematol.2021.279672
Alternate JournalHaematologica
PubMed ID35021602