Publications by authors named "Frederic Baleydier"

Despite the progress in cure rates for pediatric cancers, several challenges remain, such as the management of diseases with poor prognosis. The efficacy of intensified chemotherapies is also accompanied by increased risks of severe acute and chronic toxicities. Thus, therapies specifically targeting tumor cells, or inhibiting oncogenic molecular aberrations, could provide more effective and less toxic treatments for pediatric cancers.

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Introduction: Childhood cancer and its treatment may lead to various health complications. Related impairment in quality of life, excess in deaths and accumulated healthcare costs are relevant. Genetic variations are suggested to contribute to the wide inter-individual variability of complications but have been used only rarely to risk-stratify treatment and follow-up care.

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Rituximab (RTX) is an anti-CD20 monoclonal antibody that targets B cells-from the immature pre-B-cell stage in the bone marrow to mature circulating B cells-while preserving stem cells and plasma cells. It is used to treat autoimmune diseases, hematological malignancies, or complications after hematopoietic stem cell transplantation (HSCT). Its safety profile is acceptable; however, a subset of patients can develop persistent hypogammaglobulinemia and associated severe complications, especially in pediatric populations.

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Article Synopsis
  • - Most children with SARS-CoV-2 have mild or no symptoms, but a small group develops a serious inflammatory condition known as MIS-C, which resembles other severe immune responses.
  • - A case study describes a boy with MIS-C who showed unusual lab results and ultimately suffered from severe complications, including fatal liver failure linked to EBV-associated HLH, despite receiving multiple treatments.
  • - The diagnosis of X-linked lymphoproliferative disease type 1 (XLP1) post-mortem suggests that doctors should consider HLH in severe MIS-C cases for better treatment strategies and genetic counseling.
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Coronavirus disease-2019 in children has been linked to various clinical presentation, from paucisymptomatic cutaneous eruptions, to multisystemic inflammatory syndrome. We report the case of an 8-year-old boy who presented with persistent fever and pancytopenia, associated to a skin rash. An extensive etiological workup showed a positive serology for severe acute respiratory syndrome coronavirus 2 and Epstein-Barr virus.

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Many primary immunodeficiencies (PIDs) are recognised as being associated with malignancies, particularly lymphoid malignancies, which represent the highest proportion of cancers occurring in conjunction with this underlying condition. When patients present with genetic errors of immunity, clinicians must often reflect on whether to manage antitumoral treatment conventionally or to take a more personalised approach, considering possible existing comorbidities and the underlying status of immunodeficiency. Recent advances in antitumoral immunotherapies, such as monoclonal antibodies, antigen-specific adoptive cell therapies or compounds with targeted effects, potentially offer significant opportunities for optimising treatment for those patients, especially with lymphoid malignancies.

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Non anemic iron deficiency (NAID) is the most common nutritional deficiency. Symptoms more frequently observed in children and adolescents include fatigue, delayed psychomotor development as well as decreased school and athletic performances. Iron treatment is effective in improving symptoms in older children and adolescents.

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Malignant or nonmalignant lymphoproliferative disorders together with repeated ear, nose, and throat infections should strongly motivate immunologic investigations. Indeed, we report a 7-year-old patient with a history of persistent abdominal symptoms along with recurrent ear, nose, and throat infections, who presented with intra-abdominal masses highly suggestive of a diagnostic of lymphoma, and who was diagnosed with activated-PI3K-delta syndrome, a recently described primary immunodeficiency prone to lymphoproliferation.

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T-cell acute lymphoblastic leukemia (T-ALL) expands in various bone marrow (BM) sites of the body. We investigated whether different BM sites could differently modulate T-ALL propagation using in vivo animal models. We observed that mouse and human T-ALL develop slowly in the BM of tail vertebrae compared with the BM from thorax vertebrae.

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Article Synopsis
  • The study examines the link between post-radiation therapy overreactions (OR) in patients and their clinical radiosensitivity, highlighting the lack of consensus on effective prediction methods since 2003.
  • Researchers collected skin biopsy samples from patients with varying degrees of OR, focusing on skin fibroblasts from different sensitivity groups and analyzing their DNA damage response after radiation.
  • Findings suggest that OR patients experience a delay in the ATM protein's activity rather than a complete repair defect, leading to a proposed classification of human radiosensitivity into three groups based on their reaction severity.
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Immune thrombocytopenic purpura is a bleeding disorder for which management remains mainly guided by platelet counts. Pediatric hematologists and emergency physicians collaborated to set up a limited intervention strategy, focusing on clinical bleeding severity irrespective of platelet counts, starting in the emergency room. We report how this strategy was safely applied for 106 consecutive children admitted for newly diagnosed immune thrombocytopenic purpura.

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Neuropilins and semaphorins are known as modulators of axon guidance, angiogenesis, and organogenesis in the developing nervous system, but have been recently evidenced as also playing a role in the immune system. Here we describe the expression and role of semaphorin 3F (SEMA3F) and its receptor neuropilin-2 (NRP2) in human T cell precursors. NRP2 and SEMA3F are expressed in the human thymus, in both lymphoid and non-lymphoid compartments.

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Development of novel therapies is critical for T-cell acute leukaemia (T-ALL). Here, we investigated the effect of inhibiting the MAPK/MEK/ERK pathway on T-ALL cell growth. Unexpectedly, MEK inhibitors (MEKi) enhanced growth of 70% of human T-ALL cell samples cultured on stromal cells independently of NOTCH activation and maintained their ability to propagate in vivo.

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T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors.

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Article Synopsis
  • Pediatric T-cell lymphoblastic lymphomas (T-LBL) are often treated using protocols designed for T-cell acute lymphoblastic leukemia (T-ALL), but identifying effective treatment strategies through molecular prognostic markers is crucial for improving patient outcomes.
  • In a study involving 54 patients, researchers found that mutations in NOTCH1/FBXW7 were present in 55% of cases and linked to significantly better survival rates.
  • The study concludes that assessing NOTCH1/FBXW7 mutations can provide an early indication for therapeutic stratification, suggesting its potential as an important prognostic marker in T-LBL.
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Cytogenetic, molecular and phenotyping features of malignant hematologic diseases succeeded in improving their management by a more accurate stratification of patients according to several groups of risk and by providing a rational for targeted therapy. Three major types of treatment (excluding cellular therapy) are currently available in onco-hematology: conventional chemotherapy, small molecules for targeted therapy and monoclonal antibodies. Conventional chemotherapy with optimization of doses and multidrug-based regimens allowed to substantially improve survival of patients and keeps a place of choice in treatment of these diseases.

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Background: Notch receptors normally play a key role in guiding a variety of cell fate decisions during development and differentiation of metazoan organisms. On the other hand, dysregulation of Notch1 signaling is associated with many different types of cancer as well as tumor angiogenesis, making Notch1 a potential therapeutic target.

Principal Findings: Here we report the in vitro activities of inhibitory Notch1 monoclonal antibodies derived from cell-based and solid-phase screening of a phage display library.

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Short-term intensive chemotherapy regimens have substantially improved the prognosis of pediatric patients with Burkitt lymphoma (BL), which now has an excellent overall outcome. However, central nervous system (CNS) involvement at diagnosis remains a poor prognostic factor, and progressive or relapsed disease in the CNS is associated with even worse outcomes. We report 3 boys aged 4, 7, and 12 years treated under the French Société Française d'Oncologie Pédiatrique LMB 89/96 protocols who presented, respectively, with CNS-/bone marrow+ stage-IV BL; CNS+ stage-IV BL; and stage-I BL.

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Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials.

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Purpose: T lymphoblastic lymphomas (T-LBL) are rare disorders of immature T cells which predominantly involve the mediastinum. Their oncogenic pathways and prognostic variables are not clear.

Experimental Design: We undertook a retrospective study of 41 cytoplasmic CD3+ T-LBL (nine cases aged <16 years) by assessing stage of maturation arrest based on T cell receptor (TCR) immunogenotyping, immunohistochemistry, and quantification of the oncogenes thought to be important in immature T cell malignancies.

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