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5 results on '"Ciccimarra M."'

1. Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse

Author

Gambacorta, V, Beretta, S, Ciccimarra, M, Zito, L, Giannetti, K, Andrisani, A, Gnani, D, Zanotti, L, Oliveira, G, Carrabba, M, Cittaro, D, Merelli, I, Ciceri, F, Di Micco, R, Vago, L, Gambacorta V., Beretta S., Ciccimarra M., Zito L., Giannetti K., Andrisani A., Gnani D., Zanotti L., Oliveira G., Carrabba M. G., Cittaro D., Merelli I., Ciceri F., Di Micco R., Vago L., Gambacorta, V, Beretta, S, Ciccimarra, M, Zito, L, Giannetti, K, Andrisani, A, Gnani, D, Zanotti, L, Oliveira, G, Carrabba, M, Cittaro, D, Merelli, I, Ciceri, F, Di Micco, R, Vago, L, Gambacorta V., Beretta S., Ciccimarra M., Zito L., Giannetti K., Andrisani A., Gnani D., Zanotti L., Oliveira G., Carrabba M. G., Cittaro D., Merelli I., Ciceri F., Di Micco R., and Vago L.

Abstract

Immune escape represents a major driver of acute myeloid leukemia (AML) reemergence after allogeneic hematopoietic cell transplantation (allo-HCT), with up to 40% of relapses prompted by nongenomic loss of HLA class II expression in leukemia cells. By integrative analysis of gene expression, DNA methylation, and chromatin accessibility in paired diagnosis/relapse primary samples and in the respective patient-derived xenografts (PDX), we identify the polycomb repressive complex 2 (PRC2) as a key epigenetic driver of this immune escape modality. We report that loss of expression of HLA class II molecules is accompanied by a PRC2-dependent reduction in chromatin accessibility. Pharmacologic inhibition of PRC2 subunits rescues HLA class II expression in AML relapses in vitro and in vivo, with consequent recovery of leukemia recognition by CD4+ T cells. Our results uncover a novel link between epigenetics and leukemia immune escape, which may rapidly translate into innovative strategies to cure or prevent AML posttransplantation relapse.

Published
2022

2. Discordance between CD4 cell count and CD4 cell percentage: implications for when to start antiretroviral therapy in HIV-1 infected children

Author

Author:, Boyd, Dunn, K, David, T, Castro, H, Gibb, D. M, Duong, T, Aboulker, J. P, Bulterys, M, Cortina, Borja, Gabiano, M, Galli, C, Giaquinto, L, Harris, C, D. R, Hughes, Mckinney, M, Mofenson, R, Moye, L, Newell, J, M. L, Pahwa, Palumbo, S, Rudin, P, Sharland, C, Shearer, M, Thompson, W, Tookey, B, Corporate Author: HIV Paediatric Prognostic Markers Collaborative Study: Osimani, P., P, Mattia, De, Manzionna, D, M, Bari, Di, Ruggeri, C, Pellegrini, M, Masi, N, Ciccia, M, Lanari, M, Venturi, M, Baldi, V, Chiriacò, F, Schumacher, P, Duse, Rf, Castagna, M, Dessi, M, Dedoni, C, Cavallini, M, Gariel, R, Sabatino, D, Pomero, G, Sticca, G, Anastasio, M, Bezzi, E, Gervaso, Mt, Chiappini, P, Paganelli, E, Cecchi, S, Bassetti, Mt, Rosso, D, Cosso, R, Bartolini, D, Gotta, M, Amoretti, C, Pinzani, C, R, Bojanin, J, Viganò, A, Giacomet, V, Schneider, L, Zuccotti, Gv, Riva, E, Giovannini, M, Ferraris, G, Liprei, R, Moretti, C, Stronati, M, Cellini, M, Del, Carmen, Ciccimarra, M, Buffolano, F, Guarino, W, Bruzzese, A, Tarallo, E, Sanfilippo, L, A, Romano, A, Rampon, O, D'Elia, R, Ruga, E, and Consolini, Rita

Subjects
Male, medicine.medical_specialty, Immunology, HIV Infections, Zidovudine, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Antiretroviral Therapy, Highly Active, Epidemiology, medicine, Immunology and Allergy, Humans, Longitudinal Studies, Child, business.industry, Proportional hazards model, Infant, medicine.disease, Prognosis, Antiretroviral therapy, United States, CD4 Lymphocyte Count, Natural history, Europe, Infectious Diseases, Child, Preschool, Practice Guidelines as Topic, Disease Progression, HIV-1, Female, business, Cohort study, medicine.drug
Abstract

Objective: Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above. Design: Data were obtained on a large group of children followed longitudinally in trials and cohort studies in Europe and the USA. Follow-up was censored 6 months after the start of any antiretroviral drug other than zidovudine monotherapy. Methods: Discordance between CD4 cell count and percentage was defined in relation to ART initiation thresholds in World Health Organization (WHO) and European paediatric treatment guidelines. The relative prognostic value of CD4 cell count and percentage for progression to AIDS/death was investigated using time-updated Cox proportional hazards models, stratified by age. Results: Among 3345 children, with a total of 21 815 pairs of CD4 measurements analysed, 980 developed AIDS and/or died after a median follow-up of 1.7 years. Over one-half of children had discordant values of CD4 cell markers at the first visit when one or both treatment thresholds were crossed and approximately one-third had the same pattern of discordance at a subsequent measurement. Models suggested that CD4 percentage had little or no prognostic value over and above that contained in CD4 cell count, irrespective of age. Conclusions: More emphasis should be placed on CD4 cell count than on CD4 percentage in deciding when to start ART in HIV-1-infected children. (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Published
2010

4. HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND BREAST-MILK

Author

The Italian Register for HIV Infection in Children Coordinators: De Martino, Tovo, M, Partecipants:, Galli, Gabiano, L, Caramia, C, G, De Mattia, D, Santis, De, Ruggeri, U, Zaniboni, M, Masi, Mg, Dell'Erba, M, Dallacasa, G, Baldi, P, Eisenstecken, F, Soresina, M, Bresciani, A, Quarta, E, Dessì, G, Corrias, C, Chiappe, A, Ibba, F, P, Gregorio, Di, Sciotto, F, Tarallo, A, Lauria, L, Sticca, F, Berrino, M, Lusardi, R, Cocchi, P, Vierucci, P, Bassetti, A, Boeri, D, E, Risso, E, Forni, L, Tondo, U, Micheletti, E, Gamberetto, G, Meo, A, Clerici, Schoeller, Magni, M, Marchisio, La, Zuccotti, P, Simoni, Gv, Giovannello, L, Ferraris, A, Altobelli, G, Mazzoni, R, Cellini, Pl, Ciccimarra, M, Esposito, F, Guarino, L, Bona, A, Giordano, G, Giaquinto, S, Portelli, C, Benaglia, V, Caselli, G, Busti, D, and Consolini, Rita

Published
1994

5. Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse.

Author

Gambacorta V, Beretta S, Ciccimarra M, Zito L, Giannetti K, Andrisani A, Gnani D, Zanotti L, Oliveira G, Carrabba MG, Cittaro D, Merelli I, Ciceri F, Di Micco R, and Vago L

Subjects
Chromatin genetics, Chromatin immunology, Epigenesis, Genetic, Hematopoietic Stem Cell Transplantation, Histocompatibility Antigens Class II biosynthesis, Histocompatibility Antigens Class II genetics, Histocompatibility Antigens Class II immunology, Humans, Recurrence, Tumor Escape genetics, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute therapy, Polycomb Repressive Complex 2 genetics, Polycomb Repressive Complex 2 immunology
Abstract

Immune escape represents a major driver of acute myeloid leukemia (AML) reemergence after allogeneic hematopoietic cell transplantation (allo-HCT), with up to 40% of relapses prompted by nongenomic loss of HLA class II expression in leukemia cells. By integrative analysis of gene expression, DNA methylation, and chromatin accessibility in paired diagnosis/relapse primary samples and in the respective patient-derived xenografts (PDX), we identify the polycomb repressive complex 2 (PRC2) as a key epigenetic driver of this immune escape modality. We report that loss of expression of HLA class II molecules is accompanied by a PRC2-dependent reduction in chromatin accessibility. Pharmacologic inhibition of PRC2 subunits rescues HLA class II expression in AML relapses in vitro and in vivo, with consequent recovery of leukemia recognition by CD4+ T cells. Our results uncover a novel link between epigenetics and leukemia immune escape, which may rapidly translate into innovative strategies to cure or prevent AML posttransplantation relapse., Significance: Loss of HLA class II expression represents a frequent mechanism of leukemia posttransplantation relapse. Here we identify PRC2 as the main epigenetic driver of this immune escape modality and show that its chemical inhibition can reinstate a proficient graft-versus-leukemia effect, providing an innovative rationale for personalized epigenetic immunotherapies. See related commentary by Köhler and Zeiser, p. 1410. This article is highlighted in the In This Issue feature, p. 1397., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2022
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