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presentation.aux

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presentation.fdb_latexmk

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 # Fdb version 3
-["biber presentation"] 1675188058 "presentation.bcf" "presentation.bbl" "presentation" 1675188207
-  "presentation.bcf" 1675188206 106744 07867c1e8c8f03d3bf49aa493861e6dc "lualatex"
+["biber presentation"] 1675188058 "presentation.bcf" "presentation.bbl" "presentation" 1675254075
+  "presentation.bcf" 1675254075 106744 07867c1e8c8f03d3bf49aa493861e6dc "lualatex"
   (generated)
   "presentation.bbl"
   "presentation.blg"
-["lualatex"] 1675188200 "/home/thomas/Documents/Présentations/presentation_these_necker/presentation.tex" "presentation.pdf" "presentation" 1675188207
+["lualatex"] 1675254068 "/home/thomas/Documents/Présentations/presentation_these_necker/presentation.tex" "presentation.pdf" "presentation" 1675254075
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-  "/home/thomas/Documents/Présentations/presentation_these_necker/presentation.tex" 1675188200 25700 37fff28071cab7446ba38c83b8a5ad22 ""
+  "/home/thomas/Documents/Présentations/presentation_these_necker/presentation.tex" 1675254068 25709 76c6ffb0ea15f640929f26db16887522 ""
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-  "presentation.aux" 1675188206 5094 3cc00995c1f63dd0bd7da077bc2e1c1b "lualatex"
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-  "presentation.nav" 1675188206 3086 86fc2204232a4cb187c993191b079852 "lualatex"
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-  "presentation.tex" 1675188200 25700 37fff28071cab7446ba38c83b8a5ad22 ""
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presentation.fls

@@ -1262,9 +1262,9 @@ INPUT ./presentation.nav
 INPUT ./presentation.nav
 INPUT ./presentation.nav
 INPUT ./presentation.nav
-OUTPUT /tmp/lua_rrtxAi
-INPUT /tmp/lua_rrtxAi
-INPUT /tmp/lua_rrtxAi
+OUTPUT /tmp/lua_PgAKzg
+INPUT /tmp/lua_PgAKzg
+INPUT /tmp/lua_PgAKzg
 INPUT ./Images/amu.png
 INPUT ./Images/amu.png
 INPUT ./Images/amu.png
@@ -1278,7 +1278,7 @@ INPUT ./Images/logo_tagc.png
 INPUT ./Images/logo_tagc.png
 INPUT ./Images/logo_tagc.png
 INPUT /home/thomas/.miktex/texmfs/data/fonts/map/pdftex/pdftex.map
-INPUT /tmp/lua_rrtxAi
+INPUT /tmp/lua_PgAKzg
 INPUT ./Images/amu.png
 INPUT ./Images/logo_tagc.png
 INPUT /home/thomas/.miktex/texmfs/data/luatex-cache/generic/fonts/otl/lmroman7-regular.luc
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 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr7.tfm
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr5.tfm
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr5.tfm
-OUTPUT /tmp/lua_cwzRTA
-INPUT /tmp/lua_cwzRTA
-INPUT /tmp/lua_cwzRTA
-INPUT /tmp/lua_cwzRTA
+OUTPUT /tmp/lua_moDPNw
+INPUT /tmp/lua_moDPNw
+INPUT /tmp/lua_moDPNw
+INPUT /tmp/lua_moDPNw
 INPUT ./Images/histogram_ages.pdf
 INPUT ./Images/histogram_ages.pdf
 INPUT ./Images/histogram_ages.pdf
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 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr9.tfm
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr6.tfm
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr6.tfm
-OUTPUT /tmp/lua_XXG8Re
-INPUT /tmp/lua_XXG8Re
-INPUT /tmp/lua_XXG8Re
-INPUT /tmp/lua_XXG8Re
+OUTPUT /tmp/lua_dQYGew
+INPUT /tmp/lua_dQYGew
+INPUT /tmp/lua_dQYGew
+INPUT /tmp/lua_dQYGew
 INPUT ./Images/buffy_coat.jpeg
 INPUT ./Images/buffy_coat.jpeg
 INPUT ./Images/buffy_coat.jpeg
 INPUT ./Images/buffy_coat.jpeg
 INPUT ./Images/buffy_coat.jpeg
 INPUT ./Images/buffy_coat.jpeg
-OUTPUT /tmp/lua_a4TQVK
-INPUT /tmp/lua_a4TQVK
-INPUT /tmp/lua_a4TQVK
-INPUT /tmp/lua_a4TQVK
+OUTPUT /tmp/lua_a2Suok
+INPUT /tmp/lua_a2Suok
+INPUT /tmp/lua_a2Suok
+INPUT /tmp/lua_a2Suok
 INPUT ./Images/buffy_coat.jpeg
 INPUT ./Images/scat_all.png
 INPUT ./Images/scat_all.png
@@ -1429,10 +1429,10 @@ INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/fdsymbol/FdSymbolC-Bo
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/fdsymbol/FdSymbolC-Book.tfm
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr8.tfm
 INPUT /home/thomas/.miktex/texmfs/install/fonts/tfm/public/cm/cmr8.tfm
-OUTPUT /tmp/lua_0CxZSV
-INPUT /tmp/lua_0CxZSV
-INPUT /tmp/lua_0CxZSV
-INPUT /tmp/lua_0CxZSV
+OUTPUT /tmp/lua_3GKged
+INPUT /tmp/lua_3GKged
+INPUT /tmp/lua_3GKged
+INPUT /tmp/lua_3GKged
 INPUT ./Images/OS_graall.png
 INPUT ./Images/os_KM_FRALLE2000.png
 INPUT ./Images/os_KM_FRALLE2000.png
@@ -1447,10 +1447,10 @@ INPUT ./Images/dev_thym.png
 INPUT ./Images/dev_thym.png
 INPUT ./Images/dev_thym.png
 INPUT ./Images/dev_thym.png
-OUTPUT /tmp/lua_ra47uV
-INPUT /tmp/lua_ra47uV
-INPUT /tmp/lua_ra47uV
-INPUT /tmp/lua_ra47uV
+OUTPUT /tmp/lua_7upRL9
+INPUT /tmp/lua_7upRL9
+INPUT /tmp/lua_7upRL9
+INPUT /tmp/lua_7upRL9
 INPUT ./Images/dev_thym.png
 INPUT ./Images/dev_thym.png
 INPUT ./Images/dev_thym.png
@@ -1501,10 +1501,10 @@ INPUT ./Images/fdt_hm.png
 INPUT ./Images/fdt_hm.png
 INPUT ./Images/fdt_hm.png
 INPUT ./Images/fdt_hm.png
-OUTPUT /tmp/lua_nQYpGR
-INPUT /tmp/lua_nQYpGR
-INPUT /tmp/lua_nQYpGR
-INPUT /tmp/lua_nQYpGR
+OUTPUT /tmp/lua_X9ETPw
+INPUT /tmp/lua_X9ETPw
+INPUT /tmp/lua_X9ETPw
+INPUT /tmp/lua_X9ETPw
 INPUT ./Images/fdt_hm.png
 INPUT ./Images/fdt_hm.png
 INPUT ./Images/fdt_hm.png
@@ -1566,23 +1566,23 @@ INPUT ./Images/CoopLALT.jpg
 INPUT ./Images/CoopLALT.jpg
 INPUT ./Images/CoopLALT.jpg
 INPUT ./Images/CoopLALT.jpg
-OUTPUT /tmp/lua_nY6ZRQ
-INPUT /tmp/lua_nY6ZRQ
-INPUT /tmp/lua_nY6ZRQ
-INPUT /tmp/lua_nY6ZRQ
+OUTPUT /tmp/lua_UGCwjZ
+INPUT /tmp/lua_UGCwjZ
+INPUT /tmp/lua_UGCwjZ
+INPUT /tmp/lua_UGCwjZ
 INPUT ./Images/CoopLALT.jpg
 INPUT ./Images/OS_graall.png
 INPUT ./Images/OS_graall.png
 INPUT ./Images/OS_graall.png
 INPUT ./Images/OS_graall.png
-OUTPUT /tmp/lua_9hxP2R
-INPUT /tmp/lua_9hxP2R
-INPUT /tmp/lua_9hxP2R
-INPUT /tmp/lua_9hxP2R
-OUTPUT /tmp/lua_kLEBbY
-INPUT /tmp/lua_kLEBbY
-INPUT /tmp/lua_kLEBbY
-INPUT /tmp/lua_kLEBbY
+OUTPUT /tmp/lua_FaO2HZ
+INPUT /tmp/lua_FaO2HZ
+INPUT /tmp/lua_FaO2HZ
+INPUT /tmp/lua_FaO2HZ
+OUTPUT /tmp/lua_oBK7uG
+INPUT /tmp/lua_oBK7uG
+INPUT /tmp/lua_oBK7uG
+INPUT /tmp/lua_oBK7uG
 INPUT ./Images/bradner_a.png
 INPUT ./Images/bradner_a.png
 INPUT ./Images/bradner_a.png
@@ -1597,20 +1597,20 @@ INPUT ./Images/tal_ins.png
 INPUT ./Images/tal_ins.png
 INPUT ./Images/tal_ins.png
 INPUT ./Images/tal_ins.png
-OUTPUT /tmp/lua_XDwD0u
-INPUT /tmp/lua_XDwD0u
-INPUT /tmp/lua_XDwD0u
-INPUT /tmp/lua_XDwD0u
-OUTPUT /tmp/lua_qKPgai
-INPUT /tmp/lua_qKPgai
-INPUT /tmp/lua_qKPgai
+OUTPUT /tmp/lua_CfCQNI
+INPUT /tmp/lua_CfCQNI
+INPUT /tmp/lua_CfCQNI
+INPUT /tmp/lua_CfCQNI
+OUTPUT /tmp/lua_tIbWdi
+INPUT /tmp/lua_tIbWdi
+INPUT /tmp/lua_tIbWdi
 INPUT ./Images/qr_code.png
 INPUT ./Images/qr_code.png
 INPUT ./Images/qr_code.png
 INPUT ./Images/qr_code.png
 INPUT ./Images/qr_code.png
 INPUT ./Images/qr_code.png
-INPUT /tmp/lua_qKPgai
+INPUT /tmp/lua_tIbWdi
 INPUT ./Images/qr_code.png
 OUTPUT presentation.nav
 OUTPUT presentation.nav

presentation.log

@@ -1,4 +1,4 @@
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  restricted system commands enabled.
  file:line:error style messages enabled.
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presentation.nav

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presentation.tex

@@ -133,7 +133,7 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 \begin{frame}
   \frametitle{\emoji{crab} Introduction LAL-T}
   \begin{itemize}
-    \item<1-> Les leucémies aiguës lymphoïdes T (LAL-T) sont des pathologies cancéreuses résultant de la \alert{tansformation maligne de lymphocytes T immatures}.
+    \item<1-> La leucémie aiguë lymphoïde T (LAL-T) est une onco-hémopathie résultant de la \alert{tansformation maligne d'un lymphocyte T immature}.
     \item<2-> Maladie rare ($\simeq$ 120 cas/an en France) pic d'incidence à l'enfance entre 5 et 10 ans.
   \end{itemize}
   \centering
@@ -144,10 +144,10 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
   \frametitle{\emoji{thermometer} Clinique}
   \begin{itemize}
     \item<1-> La survenue des symptomes est brutale (aiguë).
-    \item<2-> Syndrome de masse impactant les fonctions de \alert{l'ensemble des lignées sanguines} (dyspnée, infection, saignement)
+    \item<2-> Envahissement médullaire impactant les fonctions de \alert{l'ensemble des lignées sanguines}
     \item[]\begin{itemize}
       \item<3-> Lignée érythrocytaire $\rightarrow$ anémie $\rightarrow$ dyspnée.
-      \item<4-> Lignée lymphocytaire et granuleuse $\rightarrow$ lymphopénie et neutropénie $\rightarrow$ infections opportunistes.
+      \item<4-> Lignées lymphocytaire et granuleuse $\rightarrow$ lymphopénie et neutropénie $\rightarrow$ infections opportunistes.
       \item<5-> Lignée mégacaryocytaire $\rightarrow$ thrombopénie $\rightarrow$ saignement.
     \end{itemize}
     \item<6-> Des localisations cutanées (leucémides), pulmonaires (leucostase), testiculaires, neurologiques ou d'autres organes
@@ -239,8 +239,8 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
       \item<1-> L'amélioration des protocoles de polychimiothérapie ne permet plus de gagner significativement en survie.
       \item<2-> Les malades réfractaires ou en rechute sont en impasse thérapeutique. 
       \item[\textbf{$\Rightarrow$}]<3-> Nouvelles approches thérapeutiques sont requises !
-      \item[\textbf{$\Rightarrow$}]<4-> Identifier les mécanismes oncogénétiques puis les cibler avec de nouvelles molécules.
-      \item[\textbf{$\Rightarrow$}]<5-> Cibler spécifiquement les voies cellulaires dérégulées et non plus indistinctement l'ensemble des cellules en cycle.
+      \item[\textbf{$\Rightarrow$}]<4-> Identifier les mécanismes oncogénétiques puis les cibler avec des molécules spécifiques.
+      \item[\textbf{$\Rightarrow$}]<5-> Spécifiques des mécanismes cellulaires dérégulées et non plus indistinctement l'ensemble des cellules en cycle.
     \end{itemize}
   \end{alertblock}
 \end{frame}
@@ -251,9 +251,9 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
     % Column 1
     \begin{column}{.5\textwidth}
       \begin{itemize}
-        \item<1-> Dans les LAL-T, la transformation maligne survient par la dérégulation de la thymopoïèse.
-        \item<2-> Des progéniteurs médullaires issus de la SCH $\rightarrow$ LT mûrs. Du commit
-        \item<3-> Afin de remplir des fonctions d'immunité acquise, le pool de LT produits par les lymphopoïèse T doit acquérire des récepteurs aux antigènes (TCR) capables de réagir uniquement au non-soi.
+        \item<1-> Dans la LAL-T, la transformation maligne survient lors de la thymopoïèse de la cellule d'origine.
+        \item<2-> Différenciation des progéniteurs médullaires issus de la SCH $\rightarrow$ LT mûrs.
+        \item<3-> Afin de remplir des fonctions d'immunité acquise, le pool de LT produits par la lymphopoïèse T doit acquérir des récepteurs aux antigènes (TCR) capables de réagir uniquement au non-soi.
       \end{itemize}
       \vfill
     \end{column}
@@ -269,30 +269,25 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 
 \begin{frame}{\emoji{drop-of-blood} Thymopoïèse}
   \begin{itemize}
-    \item<1-> Au niveau moléculaire, cette diversification est orchestrée épigénétiquement, produit une séquence nouvelle d'ADN, unique pour chaque lymphocyte T.
+    \item<1-> Au niveau moléculaire, cette différenciation est orchestrée épigénétiquement, produit une séquence nouvelle d'ADN, unique pour chaque lymphocyte T.
     \item<2-> Suivie par étapes de sélection et de prolifération.
-    % \item<3-> On distingue 
-    % \item<4-> \beta-selection puis réarrangement \alpha
-    % \item<5-> sélection positive et négative
   \end{itemize}
   \centering
-    \includegraphics<2>[width=.6\textwidth]{Images/TCRBschema.jpg}
-    \includegraphics<3>[width=.6\textwidth]{Images/MaturLt.png}
-    \includegraphics<4>[width=.6\textwidth]{Images/AffinityModel.jpg}
+    \includegraphics<1>[width=.6\textwidth]{Images/TCRBschema.jpg}
+    \includegraphics<2>[width=.6\textwidth]{Images/MaturLt.png}
+    \includegraphics<3>[width=.6\textwidth]{Images/AffinityModel.jpg}
 \end{frame}
 
 \begin{frame}{\emoji{dna} Altérations génomiques, paysage mutationnel}
   \begin{itemize}
     \item<1-> Les réarrangements subits par le génome des thymocytes sont pourvoyeurs d'erreurs, \alert{instabilité génétique}.
+    Entrainent rarement des mutations reponsables de la divergence du thymocyte et de son autonomisation.
     \item<2-> Les \alert{altérations somatiques/acquises} observées dans les génomes des blastes T sont catégorisables en deux groupes:
     \item[]<3->\begin{itemize}
       \item[-]<3-> Les variants de séquence (mutations ponctuelles/SNV)  
-      \item[-]<4-> Les variants de structure (SV, translocations, insertions, délétions, in.dels)
+      \item[-]<4-> Les variants de structure (SV, translocations, insertions, délétions, in/dels)
     \end{itemize}
   \end{itemize}
-  % \centering
-  %   \includegraphics<1>[width=.36\textwidth]{Images/rtmlpa_circos.pdf}
-  %   \includegraphics<2->[width=.8\textwidth]{Images/trd_trl.png}
 \end{frame}
 
 \begin{frame}{\emoji{dna} Altérations génomiques, paysage mutationnel}
@@ -330,7 +325,7 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 \begin{frame}{\emoji{horizontal-traffic-light} Type 1: onco-transcriptome}
   % \begin{itemize}
     % \item 
-    Dans les LAL-T on observe un onco-transcriptome (spécifique blastes) avec expression dérégulée et ectopique de FdT.
+    Dans les LAL-T on observe un onco-transcriptome avec expression dérégulée et ectopique de quelques FdT.
   % \end{itemize}
 
   \begin{tikzpicture}
@@ -488,8 +483,8 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 
 \begin{frame}
   \frametitle{\emoji{round-pushpin}Type 2 -- Mutations ponctuelles -- \textit{NOTCH1}}
-  La recherche au diagnostic de ces mutations est utile pour établir le pornostic.\\
-  Les mutations activatrices de \textit{NOTCH1} et perte de fonction de son inhibiteur \textit{FBXW7} délimitent un sous-groupe plus sensible à la chimiothérapie\footnotemark[1].
+  La recherche au diagnostic de ces mutations est utile pour établir le \alert{pornostic} au diagnostic.\\
+  Les mutations activatrices de \textit{NOTCH1} et perte de fonction de son inhibiteur \textit{FBXW7} délimitent un sous-groupe \alert{plus sensible à la chimiothérapie}\footnotemark[1].
   \begin{figure}
     \includegraphics[width=.4\textwidth]{Images/OS_graall.png}
   \end{figure}
@@ -499,9 +494,10 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 {\setbeamercolor{background canvas}{bg=bgturq}
 \begin{frame}[c]
   \metroset{block=fill}
+  \vspace{1cm}
   \begin{alertblock}{\emoji{thinking-face} {\centering \large Limites des connaissances} }
     \begin{itemize}
-      \item[] Dans plus d'un tiers des cas, le mécanisme de dérégulation de l'oncogène est inconnu.
+      \item[] Dans plus d'un tiers des cas, le \alert{mécanisme de dérégulation} du FdT est inconnu.
     \end{itemize}
   \end{alertblock}
 \end{frame}
@@ -509,12 +505,11 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 
 \begin{frame}{\emoji{compass} Pistes -- épigénétiques, néo-enhanceurs}
   \begin{itemize}
-    \item<1-> La régulation de l'expression génétique est principalement le résultat de certaines séquences intergéniques spécifiques.
-    \item<2-> Il a été montré l'acquisition par les cellules tumorales de néo-enhanceurs\footnotemark[1] par mutation de séquence inter-génique permettant 
-    fixation de FdT.
+    \item<1-> La régulation de l'expression des gènes est principalement le résultat de certaines \alert{séquences intergéniques}: promoteurs, enhanceurs, isolateurs...
+    \item<2-> Il a été observé dans le génome de certaines cellules tumorales la présence de mutations au niveau de séquences inter-géniques induisant la modification de l'expression normale des gènes: néo-enhanceurs\footnotemark[1].
   \end{itemize}
     \centering
-    \includegraphics<2>[width=.75\textwidth]{Images/bradner_a.png}
+    \includegraphics<2>[width=.7\textwidth]{Images/bradner_a.png}
   \footnotetext[1]{Bradner JE, et al. Cancer. Cell. 2017 Feb 9;168(4):629-643}
 \end{frame}
 
@@ -533,10 +528,10 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
 \begin{frame}[c]
   \metroset{block=fill}
   \vspace{1cm}
-  \begin{alertblock}{{\centering \large Résumé -- Rationnel} }
+  \begin{alertblock}{\centering \large Résumé -- Rationnel}
     \begin{itemize}
-      \item<1-> Dans les LAL-T on constate la \alert{dérégulation de proto-oncogènes} responsables du blocage de maturation.
-      \item<2-> En appliquant les techniques de caractérisations actuelles, dans plus d'un tiers des cas, le \alert{mécanisme de dérégulation reste inconnu}.
+      \item<1-> Dans les LAL-T on constate l'\alert{expression ectopique de FdT} empêchant le deroulement physiologique de la thymopoïèse.
+      \item<2-> En appliquant les techniques de génétique actuelles, dans plus d'un tiers des cas, le \alert{mécanisme de dérégulation reste inconnu}.
       \item<3-> Il a été montré que des mutations sur des séquences inter-géniques peuvent entraîner la \alert{formation de neo-enhancers}
       et ainsi déréguler en cis des proto-oncogènes (onco-enhancers).
       \item<4-> Cette compréhension nous permet \alert{d'envisager des thérapies ciblées} éventuellement plus efficaces avec moins d'effets secondaires.
@@ -551,10 +546,10 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
   \vspace{.6cm}
   \begin{alertblock}{\centering \large Hypothèses}
     \begin{itemize}
-      \item[A]<1-> Il serait possible par une approche \alert{pan-génique} de trouver de nombreuses mutations somatiques inter-géniques corrélèes 
-      à la dérégulation en cis des gènes adjacents (corrélation transcriptome RNA-seq, ChIP-seq).
+      \item[A]<1-> Il serait possible par une approche \alert{pan-génique} de trouver de nombreuses \alert{mutations somatiques inter-géniques corrélèes 
+      à la dérégulation en cis des gènes adjacents} (corrélation transcriptome RNA-seq, ChIP-seq).
       \item[B]<2-> Il est probable que ces \alert{altérations génétiques soient nécessaires et suffisantes} à la dérégulation en cis de gènes adjacents (expériences fonctionnelles).
-      \item[C]<3-> La majorité de ces gènes dérégulés devraient être des oncogènes connus, d'autres pourraient être de caractérisé comme des \alert{nouveaux oncogènes} (discovery).
+      \item[C]<3-> La majorité de ces gènes dérégulés devraient être des oncogènes connus, d'autres pourraint être caractérisé comme des \alert{nouveaux oncogènes} (discovery).
       \item[D]<4-> Ces altérations, pourraients permettre de stratifier les malades en groupes partageant des \alert{pronostics homogènes et distincts}.
       \item[E]<5-> La \alert{caractérisation des mécanismes de dérégulation et des oncogènes} découverts devrait permettre de trouver des vulnérabilités 
       ciblable par un traitement.
@@ -570,31 +565,29 @@ personalized treatment of t-cell acute lymphoblastic leukemia.}
     \item<2-> Actuellement 260+ RNA-seq / 70+ ChIP-seq réalisées.
     \item<3-> Analyse bio-informatique ChIP H3K27ac et H3K4me3: Yasmina Kermezli et Guillaume Charbonnier.
     \item[]<3-> $\longrightarrow$ Liste de potentiel néo-enhanceur après élimination des polymorphismes.
-    \item[]<4-> Insertion dans le locus \textit{HOXA} NC\_000007.14:27192552.
+    \item[]<4-> Insertion dans le locus \textit{HOXA} NC\_000007.14:27192552 (patient KMT2A-).
   \end{itemize}
   \vfill
   \begin{itemize}
-    \item<5-> Confirmation des mutations en Sanger et description du pipeline.
+    \item<5-> Confirmation des mutations en Sanger/LRS et description du pipeline (en cours).  
   \end{itemize}
 \end{frame}
 
-\begin{frame}{\emoji{dart} Première année de thèse -- Confirmation de l'hypothèse B}
-  \begin{itemize}
-    \item Pour l'instant pas de nouveaux potentiels oncogènes.
-  \end{itemize}
-  \vfill
-\end{frame}
 
-\begin{frame}{\emoji{dart} Deuxième année de thèse -- Hypothèses C et D}
+\begin{frame}{\emoji{dart}\emoji{dart} Deuxième année de thèse -- Hypothèses B et C}
   \begin{itemize}
-    \item<1-> Edition du génome additive et soustractive (CRISPR/CRISPRi).
-    \item<2-> Validation biologique de l'activité enhancer et éventuellement de l'activité oncogène si on trouve des nouveaux oncogènes
+    \item<1-> Edition du génome additive et soustractive (CRISPR/CRISPRi, altérations génétiques nécessaires et suffisantes ).
+    \item<2-> Validation biologique de l'activité enhanceur (néo-enhanceur, B) et éventuellement de l'activité oncogène si on trouve des nouveaux oncogènes potentiels (onco-enhanceurs, C)
+    \item[] \begin{itemize}
+      \item<3-> Pour l'instant pas de nouveaux oncogènes potentiels.
+    \end{itemize}
   \end{itemize}
 \end{frame}
 
-\begin{frame}{\emoji{dart} Troisième année de thèse -- Hypothèses E et F}
+
+\begin{frame}{\emoji{dart}\emoji{dart}\emoji{dart} Troisième année de thèse -- Hypothèses E et F}
   \begin{itemize}
-   \item Selon les oncogènes identifiés lors des étapes précédentes nous explorerons les possibles interventions thérapeutiques
+   \item Selon les oncogènes identifiés lors des étapes précédentes nous explorerons les possibles interventions pharmacologiques.
    \item Possibilité de test phramacologiques \textit{ex vivo} et \textit{in vivo}. 
   \end{itemize}
 \end{frame}