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Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Fondazione Ferrata Storti
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521248/ https://www.ncbi.nlm.nih.gov/pubmed/35021602 http://dx.doi.org/10.3324/haematol.2021.279672 |
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author | Hoff, Fieke W. van Dijk, Anneke D. Qiu, Yihua Hu, Chenyue W. Ries, Rhonda E. Ligeralde, Andrew Jenkins, Gaye N. Gerbing, Robert B. Gamis, Alan S. Aplenc, Richard Kolb, E. Anders Alonzo, Todd A. Meshinchi, Soheil Qutub, Amina A. de Bont, Eveline S.J.M. Horton, Terzah M. Kornblau, Steven M. |
author_facet | Hoff, Fieke W. van Dijk, Anneke D. Qiu, Yihua Hu, Chenyue W. Ries, Rhonda E. Ligeralde, Andrew Jenkins, Gaye N. Gerbing, Robert B. Gamis, Alan S. Aplenc, Richard Kolb, E. Anders Alonzo, Todd A. Meshinchi, Soheil Qutub, Amina A. de Bont, Eveline S.J.M. Horton, Terzah M. Kornblau, Steven M. |
author_sort | Hoff, Fieke W. |
collection | PubMed |
description | 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 patients’ samples and 30 control CD34(+) cell samples, using reverse phase protein arrays with 296 strictly validated antibodies. The multistep MetaGalaxy analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein expression patterns. PrSIG were associated with cytogenetics and mutational state, and with favorable or unfavorable prognosis. Analysis based on treatment (i.e., ADE vs. ADE plus bortezomib) identified three PrSIG that did better with ADE plus bortezomib than with ADE alone. When PrSIG were studied in the context of cytogenetic risk groups, PrSIG 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 PrSIG. Certain proteins significantly differentially expressed from normal could be identified, forming a hypothetical platform for personalized medicine. |
format | Online Article Text |
id | pubmed-9521248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-95212482022-10-24 Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study Hoff, Fieke W. van Dijk, Anneke D. Qiu, Yihua Hu, Chenyue W. Ries, Rhonda E. Ligeralde, Andrew Jenkins, Gaye N. Gerbing, Robert B. Gamis, Alan S. Aplenc, Richard Kolb, E. Anders Alonzo, Todd A. Meshinchi, Soheil Qutub, Amina A. de Bont, Eveline S.J.M. Horton, Terzah M. Kornblau, Steven M. Haematologica Article - Acute Myeloid Leukemia 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 patients’ samples and 30 control CD34(+) cell samples, using reverse phase protein arrays with 296 strictly validated antibodies. The multistep MetaGalaxy analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein expression patterns. PrSIG were associated with cytogenetics and mutational state, and with favorable or unfavorable prognosis. Analysis based on treatment (i.e., ADE vs. ADE plus bortezomib) identified three PrSIG that did better with ADE plus bortezomib than with ADE alone. When PrSIG were studied in the context of cytogenetic risk groups, PrSIG 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 PrSIG. Certain proteins significantly differentially expressed from normal could be identified, forming a hypothetical platform for personalized medicine. Fondazione Ferrata Storti 2022-01-13 /pmc/articles/PMC9521248/ /pubmed/35021602 http://dx.doi.org/10.3324/haematol.2021.279672 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article - Acute Myeloid Leukemia Hoff, Fieke W. van Dijk, Anneke D. Qiu, Yihua Hu, Chenyue W. Ries, Rhonda E. Ligeralde, Andrew Jenkins, Gaye N. Gerbing, Robert B. Gamis, Alan S. Aplenc, Richard Kolb, E. Anders Alonzo, Todd A. Meshinchi, Soheil Qutub, Amina A. de Bont, Eveline S.J.M. Horton, Terzah M. Kornblau, Steven M. Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study |
title | Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study |
title_full | Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study |
title_fullStr | Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study |
title_full_unstemmed | Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study |
title_short | Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study |
title_sort | clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a children’s oncology group study |
topic | Article - Acute Myeloid Leukemia |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521248/ https://www.ncbi.nlm.nih.gov/pubmed/35021602 http://dx.doi.org/10.3324/haematol.2021.279672 |
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