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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.913487/full |
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| author | Giulia Veltri Giulia Veltri Federica Lovisa Giuliana Cortese Marta Pillon Elisa Carraro Simone Cesaro Massimo Provenzi Salvatore Buffardi Samuela Francescato Alessandra Biffi Alessandra Biffi Barbara Buldini Barbara Buldini Valentino Conter Valentina Serafin Valentina Serafin Lara Mussolin Lara Mussolin |
| author_facet | Giulia Veltri Giulia Veltri Federica Lovisa Giuliana Cortese Marta Pillon Elisa Carraro Simone Cesaro Massimo Provenzi Salvatore Buffardi Samuela Francescato Alessandra Biffi Alessandra Biffi Barbara Buldini Barbara Buldini Valentino Conter Valentina Serafin Valentina Serafin Lara Mussolin Lara Mussolin |
| author_sort | Giulia Veltri |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T22:13:47Z |
| format | Article |
| id | doaj.art-dd79b877e63b49f39d330a4f128b241d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T22:13:47Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-dd79b877e63b49f39d330a4f128b241d2022-12-22T02:27:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.913487913487Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic LeukemiaGiulia Veltri0Giulia Veltri1Federica Lovisa2Giuliana Cortese3Marta Pillon4Elisa Carraro5Simone Cesaro6Massimo Provenzi7Salvatore Buffardi8Samuela Francescato9Alessandra Biffi10Alessandra Biffi11Barbara Buldini12Barbara Buldini13Valentino Conter14Valentina Serafin15Valentina Serafin16Lara Mussolin17Lara Mussolin18Maternal and Child Health Department, University of Padova, Padova, ItalyOncohematology, Stem Cell Transplant and Gene Therapy Research Area, Istituto di Ricerca Pediatrica Città della Speranza, Padova, ItalyOncohematology, Stem Cell Transplant and Gene Therapy Research Area, Istituto di Ricerca Pediatrica Città della Speranza, Padova, ItalyDepartment of Statistical Sciences, University of Padova, Padova, ItalyClinic of Pediatric Oncohematology, University Hospital of Padova, Padova, ItalyClinic of Pediatric Oncohematology, University Hospital of Padova, Padova, ItalyPediatric Hematology-Oncology, Woman and Child Hospital, Azienda Ospedaliera Universitaria Integrata, Verona, ItalyPediatric Hematology and Oncology Unit, Papa Giovanni XXIII Hospital, Bergamo, ItalyPediatric Haemato-Oncology Department, Santobono-Pausilipon Children’s Hospital, Napoli, ItalyMaternal and Child Health Department, University of Padova, Padova, ItalyMaternal and Child Health Department, University of Padova, Padova, ItalyClinic of Pediatric Oncohematology, University Hospital of Padova, Padova, ItalyMaternal and Child Health Department, University of Padova, Padova, ItalyClinic of Pediatric Oncohematology, University Hospital of Padova, Padova, ItalyPediatric Hematology Oncology Unit, University of Milano-Bicocca, Monza e Brianza per il Bambino e la sua Mamma (MBBM) Foundation, Azienda Socio Sanitaria Territoriale (ASST) Monza, Monza, ItalyOncohematology, Stem Cell Transplant and Gene Therapy Research Area, Istituto di Ricerca Pediatrica Città della Speranza, Padova, ItalyDepartment of Surgery Oncology and Gastroenterology, Oncology and Immunology Section, University of Padova, Padova, ItalyMaternal and Child Health Department, University of Padova, Padova, ItalyOncohematology, Stem Cell Transplant and Gene Therapy Research Area, Istituto di Ricerca Pediatrica Città della Speranza, Padova, ItalyT-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.https://www.frontiersin.org/articles/10.3389/fonc.2022.913487/fullT-LBLT-ALLphosphoproteomics analysisAKT/mTORJAK/STAT (janus kinase/signal transducer and activator of transcription) |
| spellingShingle | Giulia Veltri Giulia Veltri Federica Lovisa Giuliana Cortese Marta Pillon Elisa Carraro Simone Cesaro Massimo Provenzi Salvatore Buffardi Samuela Francescato Alessandra Biffi Alessandra Biffi Barbara Buldini Barbara Buldini Valentino Conter Valentina Serafin Valentina Serafin Lara Mussolin Lara Mussolin Phosphoproteomic Analysis Reveals a Different Proteomic Profile in Pediatric Patients With T-Cell Lymphoblastic Lymphoma or T-Cell Acute Lymphoblastic Leukemia Frontiers in Oncology T-LBL T-ALL phosphoproteomics analysis AKT/mTOR JAK/STAT (janus kinase/signal transducer and activator of transcription) |
| 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 | T-LBL T-ALL phosphoproteomics analysis AKT/mTOR JAK/STAT (janus kinase/signal transducer and activator of transcription) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.913487/full |
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