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Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia

T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) arise from the transformation of precursor T-cells sharing common morphological and immunophenotypic features. Despite this, T-LBL and T-ALL show different genomic/transcriptomic profiles and whether they represent two distinct...

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Autores principales: Veltri, Giulia, Lovisa, Federica, Cortese, Giuliana, Pillon, Marta, Carraro, Elisa, Cesaro, Simone, Provenzi, Massimo, Buffardi, Salvatore, Francescato, Samuela, Biffi, Alessandra, Buldini, Barbara, Conter, Valentino, Serafin, Valentina, Mussolin, Lara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304622/
https://www.ncbi.nlm.nih.gov/pubmed/35875136
http://dx.doi.org/10.3389/fonc.2022.913487
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author Veltri, Giulia
Lovisa, Federica
Cortese, Giuliana
Pillon, Marta
Carraro, Elisa
Cesaro, Simone
Provenzi, Massimo
Buffardi, Salvatore
Francescato, Samuela
Biffi, Alessandra
Buldini, Barbara
Conter, Valentino
Serafin, Valentina
Mussolin, Lara
author_facet Veltri, Giulia
Lovisa, Federica
Cortese, Giuliana
Pillon, Marta
Carraro, Elisa
Cesaro, Simone
Provenzi, Massimo
Buffardi, Salvatore
Francescato, Samuela
Biffi, Alessandra
Buldini, Barbara
Conter, Valentino
Serafin, Valentina
Mussolin, Lara
author_sort Veltri, Giulia
collection PubMed
description T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) arise from the transformation of precursor T-cells sharing common morphological and immunophenotypic features. Despite this, T-LBL and T-ALL show different genomic/transcriptomic profiles and whether they represent two distinct disease entities or variant manifestations of the same disease is still a matter of debate. In this work, we performed a Reverse Phase Protein Array study on T-LBL and T-ALL samples and demonstrated that they are characterized by a different phosphoproteomic profile. Indeed, T-LBLs showed the hyperactivation of FAK/ERK1/2 and AKT/mTOR pathways, whereas JAK/STAT pathway was significantly hyperphosphorylated in T-ALLs. Moreover, since the only criteria for discriminating T-LBL from T-ALL is blasts’ infiltration below 25% in the bone marrow and lymphoma patients can present with a percentage of blasts close to this cut-off, a biomarker that could help distinguishing the two diseases would be of great help for the clinical diagnosis and treatment decision. Pursuing this aim, we identified a proteomic signature of six proteins whose expression/activation was able to discriminate stage IV T-LBL from T-ALL. Moreover, we demonstrated that AKT hyperphosphorylation alone was able to distinguish stage IV T-LBL from both T-ALL and stage III T-LBL. Concluding, these data demonstrate that T-ALL and T-LBL bear different phosphoproteomic profiles, further sustaining the hypothesis of the two disease as different entities and paving the way for the identification of new biomarkers able to distinguish stage IV T-LBL from T-ALL disease, so far based only on BM involvement criteria.
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spelling pubmed-93046222022-07-23 Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia Veltri, Giulia Lovisa, Federica Cortese, Giuliana Pillon, Marta Carraro, Elisa Cesaro, Simone Provenzi, Massimo Buffardi, Salvatore Francescato, Samuela Biffi, Alessandra Buldini, Barbara Conter, Valentino Serafin, Valentina Mussolin, Lara Front Oncol Oncology T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) arise from the transformation of precursor T-cells sharing common morphological and immunophenotypic features. Despite this, T-LBL and T-ALL show different genomic/transcriptomic profiles and whether they represent two distinct disease entities or variant manifestations of the same disease is still a matter of debate. In this work, we performed a Reverse Phase Protein Array study on T-LBL and T-ALL samples and demonstrated that they are characterized by a different phosphoproteomic profile. Indeed, T-LBLs showed the hyperactivation of FAK/ERK1/2 and AKT/mTOR pathways, whereas JAK/STAT pathway was significantly hyperphosphorylated in T-ALLs. Moreover, since the only criteria for discriminating T-LBL from T-ALL is blasts’ infiltration below 25% in the bone marrow and lymphoma patients can present with a percentage of blasts close to this cut-off, a biomarker that could help distinguishing the two diseases would be of great help for the clinical diagnosis and treatment decision. Pursuing this aim, we identified a proteomic signature of six proteins whose expression/activation was able to discriminate stage IV T-LBL from T-ALL. Moreover, we demonstrated that AKT hyperphosphorylation alone was able to distinguish stage IV T-LBL from both T-ALL and stage III T-LBL. Concluding, these data demonstrate that T-ALL and T-LBL bear different phosphoproteomic profiles, further sustaining the hypothesis of the two disease as different entities and paving the way for the identification of new biomarkers able to distinguish stage IV T-LBL from T-ALL disease, so far based only on BM involvement criteria. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9304622/ /pubmed/35875136 http://dx.doi.org/10.3389/fonc.2022.913487 Text en Copyright © 2022 Veltri, Lovisa, Cortese, Pillon, Carraro, Cesaro, Provenzi, Buffardi, Francescato, Biffi, Buldini, Conter, Serafin and Mussolin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Veltri, Giulia
Lovisa, Federica
Cortese, Giuliana
Pillon, Marta
Carraro, Elisa
Cesaro, Simone
Provenzi, Massimo
Buffardi, Salvatore
Francescato, Samuela
Biffi, Alessandra
Buldini, Barbara
Conter, Valentino
Serafin, Valentina
Mussolin, Lara
Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia
title Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia
title_full Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia
title_fullStr Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia
title_full_unstemmed Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia
title_short Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia
title_sort phosphoproteomic analysis reveals a different proteomic profile in pediatric patients with t-cell lymphoblastic lymphoma or t-cell acute lymphoblastic leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304622/
https://www.ncbi.nlm.nih.gov/pubmed/35875136
http://dx.doi.org/10.3389/fonc.2022.913487
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