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Deficient necroptosis pathway as a negative prognostic factor in acute myeloid leukemia

Authors :
Antonella Padella
Sarah Parisi
Carmen Baldazzi
Eugenio Fonzi
Nicoletta Testoni
Giovanni Marconi
Maria Chiara Fontana
Valentina Robustelli
Cristina Papayannidis
Luca Bertamini
Anna Maria Ferrari
Andrea Ghelli Luserna di Rorà
Silvia Lo Monaco
Jacopo Nanni
Eugenia Franchini
Giovanni Martinelli
Emanuela Ottaviani
Stefania Paolini
Maria Chiara Abbenante
Giorgia Simonetti
LO MONACO, Silvia
Marconi, Giovanni
Fontana, MARIA CHIARA
Papayannidis, Cristina
Fonzi, Eugenio
Baldazzi, Carmen
Testoni, Nicoletta
Ottaviani, Emanuela
Franchini, Eugenia
Ferrari, Anna
Simonetti, Giorgia
Padella, Antonella
GHELLI LUSERNA DI RORÀ, Andrea
Robustelli, Valentina
Paolini, Stefania
Abbenante, Mariachiara
Parisi, Sarah
Nanni, Jacopo
Bertamini, Luca
Martinelli, Giovanni
Publication Year :
2017

Abstract

11611 Background: Necroptosis is a type of necrotic cell death involving several genes transcription and activation of molecular mechanisms as death receptors, interferon, toll-like receptors, intracellular RNA and DNA sensors.The process is leading by the family of receptor-interacting protein kinase ( RIPK3, RIPK2, RIPK1) and the MLKL substrate. Losses of RIPK3 or MLKL, as well as deficiency in apoptosis, could allow tumor cells to escape the immunomediated cells death (ICD). Methods: We performed SNP Arrays (Cytoscan HD and SNP 6.0, Affymetrix) on a cohort of 300 non-M3 AML patients at diagnosis and we analyzed the Overall Survival (OS) of our patients with deficiency on necroptosis pathways. Survival was analyzed with Kaplan-Mayer method and Log-Rank test. We further analyze the relevance of different prognostic factors by the use of COX-Hazard Ratio statistical analysis. Results: We find that 18 patients presented a loss of RIPK1 or MLKL (nobody presented losses in RIPK3/RIPK2) and 13/18 patients were older than 65 years old. The Overall Survival (OS) of patients with alterations in these genes is significantly lower than control group, with a median OS of 3 vs 6 month respectively (p

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....984011e5aa95b5d43fa163733f312947