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Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes

Myelodysplastic syndrome (MDS) is a hematological disorder characterized by abnormal stem cell differentiation and a high risk of acute myeloid leukemia transformation. Treatment options for MDS are still limited, making the identification of molecular signatures for MDS progression a vital task. Th...

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Autores principales: Moura, Arlindo A., Bezerra, Maria Julia B., Martins, Aline M. A., Borges, Daniela P., Oliveira, Roberta T. G., Oliveira, Raphaela M., Farias, Kaio M., Viana, Arabela G., Carvalho, Guilherme G. C., Paier, Carlos R. K., Sousa, Marcelo V., Fontes, Wagner, Ricart, Carlos A. O., Moraes, Maria Elisabete A., Magalhães, Silvia M. M., Furtado, Cristiana L. M., Moraes-Filho, Manoel O., Pessoa, Claudia, Pinheiro, Ronald F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257025/
https://www.ncbi.nlm.nih.gov/pubmed/35814389
http://dx.doi.org/10.3389/fonc.2022.833068
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author Moura, Arlindo A.
Bezerra, Maria Julia B.
Martins, Aline M. A.
Borges, Daniela P.
Oliveira, Roberta T. G.
Oliveira, Raphaela M.
Farias, Kaio M.
Viana, Arabela G.
Carvalho, Guilherme G. C.
Paier, Carlos R. K.
Sousa, Marcelo V.
Fontes, Wagner
Ricart, Carlos A. O.
Moraes, Maria Elisabete A.
Magalhães, Silvia M. M.
Furtado, Cristiana L. M.
Moraes-Filho, Manoel O.
Pessoa, Claudia
Pinheiro, Ronald F.
author_facet Moura, Arlindo A.
Bezerra, Maria Julia B.
Martins, Aline M. A.
Borges, Daniela P.
Oliveira, Roberta T. G.
Oliveira, Raphaela M.
Farias, Kaio M.
Viana, Arabela G.
Carvalho, Guilherme G. C.
Paier, Carlos R. K.
Sousa, Marcelo V.
Fontes, Wagner
Ricart, Carlos A. O.
Moraes, Maria Elisabete A.
Magalhães, Silvia M. M.
Furtado, Cristiana L. M.
Moraes-Filho, Manoel O.
Pessoa, Claudia
Pinheiro, Ronald F.
author_sort Moura, Arlindo A.
collection PubMed
description Myelodysplastic syndrome (MDS) is a hematological disorder characterized by abnormal stem cell differentiation and a high risk of acute myeloid leukemia transformation. Treatment options for MDS are still limited, making the identification of molecular signatures for MDS progression a vital task. Thus, we evaluated the proteome of bone marrow plasma from patients (n = 28) diagnosed with MDS with ring sideroblasts (MDS-RS) and MDS with blasts in the bone marrow (MDS-EB) using label-free mass spectrometry. This strategy allowed the identification of 1,194 proteins in the bone marrow plasma samples. Polyubiquitin-C (UBC), moesin (MSN), and Talin-1 (TLN1) showed the highest abundances in MDS-EB, and centrosomal protein of 55 kDa (CEP55) showed the highest relative abundance in the bone marrow plasma of MDS-RS patients. In a follow-up, in the second phase of the study, expressions of UBC, MSN, TLN1, and CEP55 genes were evaluated in bone marrow mononuclear cells from 45 patients by using qPCR. This second cohort included only seven patients from the first study. CEP55, MSN, and UBC expressions were similar in mononuclear cells from MDS-RS and MDS-EB individuals. However, TLN1 gene expression was greater in mononuclear cells from MDS-RS (p = 0.049) as compared to MDS-EB patients. Irrespective of the MDS subtype, CEP55 expression was higher (p = 0.045) in MDS patients with abnormal karyotypes, while MSN, UBC, and TALIN1 transcripts were similar in MDS with normal vs. abnormal karyotypes. In conclusion, proteomic and gene expression approaches brought evidence of altered TLN1 and CEP55 expressions in cellular and non-cellular bone marrow compartments of patients with low-risk (MDS-RS) and high-risk (MDS-EB) MDSs and with normal vs. abnormal karyotypes. As MDS is characterized by disrupted apoptosis and chromosomal alterations, leading to mitotic slippage, TLN1 and CEP55 represent potential markers for MDS prognosis and/or targeted therapy.
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spelling pubmed-92570252022-07-07 Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes Moura, Arlindo A. Bezerra, Maria Julia B. Martins, Aline M. A. Borges, Daniela P. Oliveira, Roberta T. G. Oliveira, Raphaela M. Farias, Kaio M. Viana, Arabela G. Carvalho, Guilherme G. C. Paier, Carlos R. K. Sousa, Marcelo V. Fontes, Wagner Ricart, Carlos A. O. Moraes, Maria Elisabete A. Magalhães, Silvia M. M. Furtado, Cristiana L. M. Moraes-Filho, Manoel O. Pessoa, Claudia Pinheiro, Ronald F. Front Oncol Oncology Myelodysplastic syndrome (MDS) is a hematological disorder characterized by abnormal stem cell differentiation and a high risk of acute myeloid leukemia transformation. Treatment options for MDS are still limited, making the identification of molecular signatures for MDS progression a vital task. Thus, we evaluated the proteome of bone marrow plasma from patients (n = 28) diagnosed with MDS with ring sideroblasts (MDS-RS) and MDS with blasts in the bone marrow (MDS-EB) using label-free mass spectrometry. This strategy allowed the identification of 1,194 proteins in the bone marrow plasma samples. Polyubiquitin-C (UBC), moesin (MSN), and Talin-1 (TLN1) showed the highest abundances in MDS-EB, and centrosomal protein of 55 kDa (CEP55) showed the highest relative abundance in the bone marrow plasma of MDS-RS patients. In a follow-up, in the second phase of the study, expressions of UBC, MSN, TLN1, and CEP55 genes were evaluated in bone marrow mononuclear cells from 45 patients by using qPCR. This second cohort included only seven patients from the first study. CEP55, MSN, and UBC expressions were similar in mononuclear cells from MDS-RS and MDS-EB individuals. However, TLN1 gene expression was greater in mononuclear cells from MDS-RS (p = 0.049) as compared to MDS-EB patients. Irrespective of the MDS subtype, CEP55 expression was higher (p = 0.045) in MDS patients with abnormal karyotypes, while MSN, UBC, and TALIN1 transcripts were similar in MDS with normal vs. abnormal karyotypes. In conclusion, proteomic and gene expression approaches brought evidence of altered TLN1 and CEP55 expressions in cellular and non-cellular bone marrow compartments of patients with low-risk (MDS-RS) and high-risk (MDS-EB) MDSs and with normal vs. abnormal karyotypes. As MDS is characterized by disrupted apoptosis and chromosomal alterations, leading to mitotic slippage, TLN1 and CEP55 represent potential markers for MDS prognosis and/or targeted therapy. Frontiers Media S.A. 2022-06-22 /pmc/articles/PMC9257025/ /pubmed/35814389 http://dx.doi.org/10.3389/fonc.2022.833068 Text en Copyright © 2022 Moura, Bezerra, Martins, Borges, Oliveira, Oliveira, Farias, Viana, Carvalho, Paier, Sousa, Fontes, Ricart, Moraes, Magalhães, Furtado, Moraes-Filho, Pessoa and Pinheiro 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
Moura, Arlindo A.
Bezerra, Maria Julia B.
Martins, Aline M. A.
Borges, Daniela P.
Oliveira, Roberta T. G.
Oliveira, Raphaela M.
Farias, Kaio M.
Viana, Arabela G.
Carvalho, Guilherme G. C.
Paier, Carlos R. K.
Sousa, Marcelo V.
Fontes, Wagner
Ricart, Carlos A. O.
Moraes, Maria Elisabete A.
Magalhães, Silvia M. M.
Furtado, Cristiana L. M.
Moraes-Filho, Manoel O.
Pessoa, Claudia
Pinheiro, Ronald F.
Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes
title Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes
title_full Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes
title_fullStr Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes
title_full_unstemmed Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes
title_short Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes
title_sort global proteomics analysis of bone marrow: establishing talin-1 and centrosomal protein of 55 kda as potential molecular signatures for myelodysplastic syndromes
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257025/
https://www.ncbi.nlm.nih.gov/pubmed/35814389
http://dx.doi.org/10.3389/fonc.2022.833068
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