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. Article, . En, and . De-révision-À-nature-medicine-annexe, CLASSIFICATION ANN ARBOR Stage I : single lymph node region (I) or single extralymphatic organ or site (IE), ANNEXES Annexe, vol.1

, Stage II : > 2 lymph node regions on same side of diaphragm (II) or with limited, contiguous extra lymphatic tissue involvement (IIE)

, Stage III : both sides of diaphragm involved, may include spleen (IIIS) or local tissue involvement (IIIE)

, Stage IV : multiple/disseminated foci involved with > 1 extralymphatic organs (i.e. bone marrow)

, Cette différence s'observe chez les patients traités par R-CHOP mais pas pour ceux traités par CHOP seul. Les objectifs de mon travail sont : i) démontrer que la GAPDH est un biomarqueur immunohistochimique (IHC) prédictif de la réponse des DLBCL au traitement actuel, le R-CHOP, ii) identifier par une approche anatomopathologique, le(s) mécanisme(s) qui relie(nt) les niveaux de GAPDH à la réponse thérapeutique au R-CHOP. Nous avons examiné l'expression IHC de la GAPDH dans 43 biopsies ganglionnaires prélevées au diagnostic de patients traités par R-CHOP entre 2008 et 2014 au CHU de Nice et à l'Hôpital Saint Louis à Paris. Nous avons réalisé un score d'expression en fonction de l'intensité du marquage et du pourcentage de cellules marquées. Nous avons ensuite déterminé un seuil permettant de classer les DLBCL en GAPDH-High (DGH) ou GAPDH-Low (DGL). Ainsi, nous avons montré que les DGH corrèlent avec une meilleure réponse au R-CHOP. À contrario, les DGL sont associés à un mauvais pronostic. En analyse multivariée, l'expression IHC de la GAPDH est un facteur pronostique indépendant des autres marqueurs pronostiques clinico-biologiques comme l'IPIaa, BCL-2, BCL-6, P53 ou MYC. La GAPDH apparait comme un facteur prédictif facile d'utilisation, indépendant des autres facteurs pronostiques. Nous avons validé notre seuil et confirmé nos résultats sur les TMA d, En dépit de l'avancée majeure des traitements avec l'immunothérapie (Rituximab, R) qui, associée à la chimiothérapie (CHOP) a augmenté la médiane de survie, 30-40% des patients atteints de DLBCL sont en échec thérapeutique. Il est donc impératif de mettre en évidence un nouveau marqueur permettant d'une part d'identifier au diagnostic les patients susceptibles d'être réfractaires à l'immuno-chimiothérapie

. Rituximab, Ces résultats suggèrent que la GAPDH, par l'intermédiaire de la régulation de l'expression de CD20, est un marqueur prédictif de la réponse au R-CHOP. La GAPDH étant une enzyme du métabolisme glycolytique, nous avons également montré qu'elle pouvait prédire l'efficacité d'une stratégie ciblant le métabolisme énergétique de la tumeur. Par conséquent, ce biomarqueur pourrait permettre i) de prédire l

, orienter des patients susceptibles d'être réfractaires au R-CHOP vers une nouvelle alternative thérapeutique

. Serment-d'hippocrate,

, de mes chers condisciples et devant l'effigie d'Hippocrate, Je promets et je jure d'être fidèle aux lois de l'honneur et de la probité dans l

, Je donnerai mes soins gratuits à l'indigent et n'exigerai jamais un salaire au-dessus de mon travail

, Admise dans l'intérieur des maisons, mes yeux ne verront pas ce qui s'y passe, ma langue taira les secrets qui me seront confiés et mon état ne servira pas à corrompre les moeurs ni à favoriser le crime

, Je ne permettrai pas que des considérations de religion, de nation, de race

, Même sous la menace, je n'admettrai pas de faire usage de mes connaissances médicales contre les lois de l'humanité

, Respectueuse et reconnaissante envers mes Maîtres, je rendrai à leurs enfants l'instruction que j'ai reçue de leurs pères

, Que les hommes m'accordent leur estime si je suis fidèle à mes promesses ! Que je sois couverte d'opprobre et méprisée de mes confrères si j'y manque