title: Localization of the NRAS:BCL-2 complex determines anti-apoptotic features associated with progressive disease in myelodysplastic syndromes.
abstract: We have previously demonstrated that two prognostic features of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML), mutant NRAS and over-expressing BCL-2, cooperate physically and functionally in vivo. Screening of MDS patient bone marrow (BM) identified NRAS:BCL-2 co-localization in 64% cases, correlating with percentage BM blasts, apoptotic features and disease status (p<0.0001). Localization of the complex at the plasma membrane or the mitochondria correlated with disease and apoptosis features in MDS patients, whilst caspase-9 mediated mechanism was elucidated in vivo and in vitro. The intensity and localization of the RAS:BCL-2 complex merits further evaluation as a novel biomarker of MDS.
authors.affiliation: INSERM U940, F-75475 Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Le Pogam
authors.forename: Patricia
authors.initials: P
authors.lastname: Krief
authors.forename: Stephanie
authors.initials: S
authors.lastname: Beurlet
authors.forename: Annie
authors.initials: A
authors.lastname: Soulié
authors.forename: Nicole
authors.initials: N
authors.lastname: Balitrand
authors.forename: Bruno
authors.initials: B
authors.lastname: Cassinat
authors.forename: Helene
authors.initials: H
authors.lastname: Cavé
authors.forename: Olivier
authors.initials: O
authors.lastname: Kosmider
authors.forename: Niclas
authors.initials: N
authors.lastname: Setterblad
authors.forename: Christophe
authors.initials: C
authors.lastname: Leboeuf
authors.forename: Laure
authors.initials: L
authors.lastname: Sarda-Mantel
authors.forename: Florence
authors.initials: F
authors.lastname: Hervatin
authors.forename: Pascal
authors.initials: P
authors.lastname: Merlet
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Noguera
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Marika
authors.initials: M
authors.lastname: Pla
authors.forename: Michaela
authors.initials: M
authors.lastname: Fontenay
authors.forename: Lionel
authors.initials: L
authors.lastname: Adès
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Padua
authors.forename: Nader
authors.initials: N
authors.lastname: Omidvar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D018631:ras Proteins