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Identifying Candidate Gene Drivers Associated with Relapse in Pediatric T-Cell Acute Lymphoblastic Leukemia Using a Gene Co-Expression Network Approach.
Kypraios, Anthony; Bennour, Juba; Imbert, Véronique; David, Léa; Calvo, Julien; Pflumio, Françoise; Bonnet, Raphaël; Couralet, Marie; Magnone, Virginie; Lebrigand, Kevin; Barbry, Pascal; Rohrlich, Pierre S; Peyron, Jean-François.
Afiliação
  • Kypraios A; Université Côte d'Azur, Inserm C3M, 06200 Nice, France.
  • Bennour J; Team#4: "Fundamental to Translational Research on Dysregulated Hematopoiesis-DysHema", Centre Méditerranéen de Médecine Moléculaire-C3M-Inserm U1065, Bâtiment Universitaire ARCHIMED, 151 Route Saint Antoine de Ginestière, BP 2 3194, CEDEX 3, 06204 Nice, France.
  • Imbert V; Université Côte d'Azur, Inserm C3M, 06200 Nice, France.
  • David L; Team#4: "Fundamental to Translational Research on Dysregulated Hematopoiesis-DysHema", Centre Méditerranéen de Médecine Moléculaire-C3M-Inserm U1065, Bâtiment Universitaire ARCHIMED, 151 Route Saint Antoine de Ginestière, BP 2 3194, CEDEX 3, 06204 Nice, France.
  • Calvo J; Université Côte d'Azur, Inserm C3M, 06200 Nice, France.
  • Pflumio F; Team#4: "Fundamental to Translational Research on Dysregulated Hematopoiesis-DysHema", Centre Méditerranéen de Médecine Moléculaire-C3M-Inserm U1065, Bâtiment Universitaire ARCHIMED, 151 Route Saint Antoine de Ginestière, BP 2 3194, CEDEX 3, 06204 Nice, France.
  • Bonnet R; Université Côte d'Azur, Inserm C3M, 06200 Nice, France.
  • Couralet M; Team#4: "Fundamental to Translational Research on Dysregulated Hematopoiesis-DysHema", Centre Méditerranéen de Médecine Moléculaire-C3M-Inserm U1065, Bâtiment Universitaire ARCHIMED, 151 Route Saint Antoine de Ginestière, BP 2 3194, CEDEX 3, 06204 Nice, France.
  • Magnone V; Université de Paris, Inserm, CEA, 92260 Fontenay-aux-Roses, France.
  • Lebrigand K; Université de Paris, Inserm, CEA, 92260 Fontenay-aux-Roses, France.
  • Barbry P; Université Côte d'Azur, Inserm C3M, 06200 Nice, France.
  • Rohrlich PS; Team#4: "Fundamental to Translational Research on Dysregulated Hematopoiesis-DysHema", Centre Méditerranéen de Médecine Moléculaire-C3M-Inserm U1065, Bâtiment Universitaire ARCHIMED, 151 Route Saint Antoine de Ginestière, BP 2 3194, CEDEX 3, 06204 Nice, France.
  • Peyron JF; Université Côte d'Azur, CNRS, IPMC, 06560 Valbonne, France.
Cancers (Basel) ; 16(9)2024 Apr 25.
Article em En | MEDLINE | ID: mdl-38730619
ABSTRACT
Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) relapses are still associated with a dismal outcome, justifying the search for new therapeutic targets and relapse biomarkers. Using single-cell RNA sequencing (scRNAseq) data from three paired samples of pediatric T-ALL at diagnosis and relapse, we first conducted a high-dimensional weighted gene co-expression network analysis (hdWGCNA). This analysis highlighted several gene co-expression networks (GCNs) and identified relapse-associated hub genes, which are considered potential driver genes. Shared relapse-expressed genes were found to be related to antigen presentation (HLA, B2M), cytoskeleton remodeling (TUBB, TUBA1B), translation (ribosomal proteins, EIF1, EEF1B2), immune responses (MIF, EMP3), stress responses (UBC, HSP90AB1/AA1), metabolism (FTH1, NME1/2, ARCL4C), and transcriptional remodeling (NF-κB family genes, FOS-JUN, KLF2, or KLF6). We then utilized sparse partial least squares discriminant analysis to select from a pool of 481 unique leukemic hub genes, which are the genes most discriminant between diagnosis and relapse states (comprising 44, 35, and 31 genes, respectively, for each patient). Applying a Cox regression method to these patient-specific genes, along with transcriptomic and clinical data from the TARGET-ALL AALL0434 cohort, we generated three model gene signatures that efficiently identified relapsed patients within the cohort. Overall, our approach identified new potential relapse-associated genes and proposed three model gene signatures associated with lower survival rates for high-score patients.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article