9 results on '"Valeria Bisio"'
Search Results
2. WHIM Syndrome-linked CXCR4 mutations drive osteoporosis
- Author
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Adrienne Anginot, Julie Nguyen, Zeina Abou Nader, Vincent Rondeau, Amélie Bonaud, Maria Kalogeraki, Antoine Boutin, Julia P. Lemos, Valeria Bisio, Joyce Koenen, Lea Hanna Doumit Sakr, Amandine Picart, Amélie Coudert, Sylvain Provot, Nicolas Dulphy, Michel Aurrand-Lions, Stéphane J. C. Mancini, Gwendal Lazennec, David H. McDermott, Fabien Guidez, Claudine Blin-Wakkach, Philip M. Murphy, Martine Cohen-Solal, Marion Espéli, Matthieu Rouleau, and Karl Balabanian
- Subjects
Science - Abstract
Abstract WHIM Syndrome is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report a decrease in bone mineral density in 25% of WHIM patients and bone defects leading to osteoporosis in a WHIM mouse model. Imbalanced bone tissue is observed in mutant mice combining reduced osteoprogenitor cells and increased osteoclast numbers. Mechanistically, impaired CXCR4 desensitization disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, while increasing their pro-osteoclastogenic capacities. Impaired osteogenic differentiation is evidenced in primary bone marrow stromal cells from WHIM patients. In mice, chronic treatment with the CXCR4 antagonist AMD3100 normalizes in vitro osteogenic fate of mutant skeletal stromal/stem cells and reverses in vivo the loss of skeletal cells, demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of skeletal stromal/stem cells. Our study provides mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of skeletal cells and the balance between bone formation and resorption.
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- 2023
- Full Text
- View/download PDF
3. Myelodysplastic Syndrome associated TET2 mutations affect NK cell function and genome methylation
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Maxime Boy, Valeria Bisio, Lin-Pierre Zhao, Fabien Guidez, Bérénice Schell, Emilie Lereclus, Guylaine Henry, Juliette Villemonteix, Fernando Rodrigues-Lima, Katia Gagne, Christelle Retiere, Lise Larcher, Rathana Kim, Emmanuelle Clappier, Marie Sebert, Arsène Mekinian, Olivier Fain, Anne Caignard, Marion Espeli, Karl Balabanian, Antoine Toubert, Pierre Fenaux, Lionel Ades, and Nicolas Dulphy
- Subjects
Science - Abstract
Myelodysplastic syndromes are characterised by clonal haematopoiesis, with the affected cells often harbouring mutations in the TET2 gene, an important regulator of DNA methylation state. Here authors show that the same mutations are also found in NK cells, perturbing their DNA methylation pattern and cytolytic function.
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- 2023
- Full Text
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4. Innate lymphoid cells: NK and cytotoxic ILC3 subsets infiltrate metastatic breast cancer lymph nodes
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Louise Rethacker, Maxime Boy, Valeria Bisio, France Roussin, Jordan Denizeau, Anne Vincent-Salomon, Edith Borcoman, Christine Sedlik, Eliane Piaggio, Antoine Toubert, Nicolas Dulphy, and Anne Caignard
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Innate lymphoid cells ,natural killer cells ,tumor draining lymph nodes ,breast cancers ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Innate lymphoid cells (ILCs) – which include cytotoxic Natural Killer (NK) cells and helper-type ILC – are important regulators of tissue immune homeostasis, with possible roles in tumor surveillance. We analyzed ILC and their functionality in human lymph nodes (LN). In LN, NK cells and ILC3 were the prominent subpopulations. Among the ILC3s, we identified a CD56+/ILC3 subset with a phenotype close to ILC3 but also expressing cytotoxicity genes shared with NK. In tumor-draining LNs (TD-LNs) and tumor samples from breast cancer (BC) patients, NK cells were prominent, and proportions of ILC3 subsets were low. In tumors and TD-LN, NK cells display reduced levels of NCR (Natural cytotoxicity receptors), despite high transcript levels and included a small subset CD127− CD56− NK cells with reduced function. Activated by cytokines CD56+/ILC3 cells from donor and patients LN acquired cytotoxic capacity and produced IFNg. In TD-LN, all cytokine activated ILC populations produced TNFα in response to BC cell line. Analyses of cytotoxic and helper ILC indicate a switch toward NK cells in TD-LN. The local tumor microenvironment inhibited NK cell functions through downregulation of NCR, but cytokine stimulation restored their functionality.
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- 2022
- Full Text
- View/download PDF
5. The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics
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Elena Porcù, Maddalena Benetton, Valeria Bisio, Ambra Da Ros, Claudia Tregnago, Giulia Borella, Carlo Zanon, Matteo Bordi, Giuseppe Germano, Sabrina Manni, Silvia Campello, Dinesh S. Rao, Franco Locatelli, and Martina Pigazzi
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Molecular biology ,Cell biology ,Cancer ,Science - Abstract
Summary: Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation.
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- 2021
- Full Text
- View/download PDF
6. Comprehensive Analysis of Mesenchymal Cells from Myeloproliferative Neoplasm (MPN) Patients Reveals the Role of HOXB7 in Myelofibrosis Induction
- Author
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Saravanan Ganesan, Sarah Awan-Toor, Fabien Guidez, Nabih Maslah, Celine Aoun, Panhong Gou, Chloe Guiguen, Juliette Soret, Odonchimeg Ravdan, Valeria Bisio, Nicolas Dulphy, Marie-Hélène Schlageter, Michele Souyri, Stephane Giraudier, Jean-Jacques Kiladjian, Christine Chomienne, and Bruno Cassinat
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
7. WHIM Syndrome-linked CXCR4 mutations drive osteoporosis by mitigating the osteogenic specification of skeletal stromal cells
- Author
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Adrienne Anginot, Julie Nguyen, Zeina Abou-Nader, Vincent Rondeau, Amélie Bonaud, Antoine Boutin, Julia Lemos, Valeria Bisio, Joyce Koenen, Léa Sakr, Caroline Marty, Amélie Coudert, Sylvain Provot, Nicolas Dulphy, Michel Aurrand-Lions, Stéphane Mancini, Gwendal lazennec, David McDermott, Fabien Guidez, Claudine Blin-Wakkach, Philip Murphy, Martine Cohen-Solal, Marion Espeli, Matthieu Rouleau, and Karl Balabanian
- Abstract
WHIM Syndrome (WS) is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report for the first time a substantial decrease in bone mineral density in 25% of WS patients and bone defects leading to osteoporosis in a WS mouse model. Reduction in bone content involved impaired CXCR4 desensitization that disrupts cell cycle progression and osteogenic specification of mouse bone marrow (BM)-residing skeletal stromal/stem cells (SSCs). This was also evidenced in BM stromal cells from WS patients. Consistent with this, chronic treatment with the CXCR4 antagonist AMD3100 normalized in vitro osteogenic fate of mutant SSCs and reversed in vivo loss in skeletal cells, thus demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of BM SSCs. Our study provides novel mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of BM SSCs.
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- 2022
8. The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics
- Author
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Martina Pigazzi, Ambra Da Ros, Elena Porcù, Sabrina Manni, Maddalena Benetton, Dinesh S. Rao, Franco Locatelli, Claudia Tregnago, Giulia Borella, Matteo Bordi, Silvia Campello, Carlo Zanon, Giuseppe Germano, and Valeria Bisio
- Subjects
Cell biology ,Myeloid ,Settore BIO/06 ,Childhood Leukemia ,Pediatric Cancer ,Cancer ,Molecular biology ,Science ,CD34 ,Biology ,Article ,chemistry.chemical_compound ,Rare Diseases ,Stem Cell Research - Nonembryonic - Human ,hemic and lymphatic diseases ,Genetics ,medicine ,2.1 Biological and endogenous factors ,Gene silencing ,Aetiology ,Pediatric ,Multidisciplinary ,Myeloid leukemia ,Hematology ,Stem Cell Research ,medicine.disease ,Haematopoiesis ,Leukemia ,medicine.anatomical_structure ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,RUNX1 ,chemistry ,Cancer research ,Cytarabine ,medicine.drug - Abstract
Summary Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation., Graphical abstract, Highlights • CDK6-AS1 acts in concert with CDK6 • High CDK6-AS1 levels trigger RUNX1 early differentiation arrest in myeloid cells • CDK6-AS1 controls mitochondrial mass of AML blasts • CDK6-AS1 levels impact on mitochondrial-targeted agents sensitivity, Molecular biology; Cell biology; Cancer
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- 2021
9. MDS-029: Prevalence of VEXAS Syndrome in MDS/CMML Patients with Systemic Inflammatory and Auto-Immune Disease
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Emmanuelle Clappier, Mohamed Bedis Dhouaieb, Pierre Lemaire, Arsène Mekinian, Lise Larcher, Nicolas Dulphy, Olivier Fain, Clémentine Chauvel, Raphael Itzykson, Marie Sebert, Lin-Pierre Zhao, Lionel Ades, Antoine Toubert, Maxime Boy, Alice Marceau-Renaut, Pierre Fenaux, Stephanie Mathis, Bérénice Schell, Valeria Bisio, Claude Preudhomme, and Rathana Kim
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Oncology ,Cancer Research ,medicine.medical_specialty ,Myeloid ,business.industry ,Azathioprine ,Context (language use) ,Retrospective cohort study ,Hematology ,Disease ,medicine.disease ,Leukemia ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Internal medicine ,Cohort ,medicine ,business ,Relapsing polychondritis ,medicine.drug - Abstract
Context: Systemic inflammatory and auto-immune diseases (SIAD) are observed in 25% of patients with MDS or CMML, who harbor a high frequency of mutations in TET2, IDH1/2 and SRSF2 as we previously reported (Zhao et al, Leukemia 2021). Recently, the identification of mutations in UBA1 in patients with autoinflammatory disorders, some of whom have dysplastic bone marrow, defined novel disease called VEXAS syndrome (Beck et al, NEJM 2020). Objective: To explore the prevalence of UBA1 mutations in our initial cohort of MDS/CMML patients with SIAD (n=85) (Zhao et al, Leukemia 2021). Design and Patients: All male patients for whom material was available (n=33) were analyzed for the presence of UBA1 mutations. Primary Outcome: UBA1 mutations screening with Sanger sequencing. Results: Four out of 33 (12%) patients had UBA1 mutations. All of them had MDS without excess of blasts. Cytomorphologic review of bone marrow smears showed numerous vacuoles in precursors in all 4 cases. Karyotype was normal in 3/4 patients, and one patient had deletion 9q. One patient also had somatic mutations in DNMT3A (VAF 11%) and TP53 (VAF 2%), and another patient had a mutation of TET2 (VAF 18%). Three patients in our MDS/CMML SIAD cohort had relapsing polychondritis, and 2 of them had UBA1 mutations, while 6 patients from our initial SIAD cohort had a diagnosis of Sweet syndrome, including 2 with UBA1 mutations. Three out of 4mut patients had steroid refractory SIAD and were heavily treated with other immunosuppressive therapies including methotrexate, azathioprine or cytokine targeting agents. At last follow-up, none of the 4 patients with UBA1 mutations had MDS progression, and one of them had died from a stroke, 2.4 years after MDS diagnosis. Conclusions: Our retrospective study represents the first assessment of VEXAS syndrome among patients with myeloid malignancies associated with SIAD. The low prevalence of UBA1 mutations in our cohort suggests that other pathological mechanisms may drive inflammation in the large majority of MDS/CMML patients with associated SIAD, likely in relation with mutations in epigenetic regulators TET2/IDH and SRSF2 as we previously proposed.
- Published
- 2021
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