{"id":15166,"date":"2021-06-24T21:00:11","date_gmt":"2021-06-24T19:00:11","guid":{"rendered":"https:\/\/convergences.online\/hemato\/?p=15166"},"modified":"2024-12-11T13:28:52","modified_gmt":"2024-12-11T12:28:52","slug":"pas-de-tp53-pas-de-reponse-aux-bh3","status":"publish","type":"post","link":"https:\/\/www.hematostat.net\/en\/pas-de-tp53-pas-de-reponse-aux-bh3\/","title":{"rendered":"Pas de TP53, pas de r\u00e9ponse aux BH3 !"},"content":{"rendered":"

R\u00e9f. : HematoStat.net ; 2 (2) : R20<\/p>\n

Thijssen R and al. Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias. Blood. 137(20), 2721-2735.<\/em><\/a><\/p>\n<\/p>\n

R\u00e9sum\u00e9<\/strong><\/h3>\n

Le v\u00e9n\u00e9toclax, traitement prometteur dans la leuc\u00e9mie, appartient \u00e0 la famille des BH3 mim\u00e9tiques, ciblant BCL2 et MCL1 et d\u00e9clenchant ainsi l\u2019apoptose mitochondriale. Des \u00e9tudes cliniques ont montr\u00e9 qu\u2019apr\u00e8s une r\u00e9ponse initiale au v\u00e9n\u00e9toclax, les patients mut\u00e9s TP53 pouvaient rechuter pr\u00e9cocement de leur LLC ou LAM, malgr\u00e9 une association aux agents d\u00e9m\u00e9thylants ou \u00e0 la chimioth\u00e9rapie. Les auteurs s\u2019int\u00e9ressent donc ici \u00e0 l\u2019impact de la dysfonction TP53 sur la r\u00e9ponse aux BH3 mim\u00e9tiques. Ils d\u00e9montrent que les clones de LAM mut\u00e9s TP53 prolif\u00e8rent avec une exposition courte de v\u00e9n\u00e9toclax. La perte de TP53 est responsable d\u2019alt\u00e9ration variable d\u2019induction d\u2019apoptose par le v\u00e9n\u00e9toclax. Ils mettent en \u00e9vidence sur des mod\u00e8les de x\u00e9nogreffe de LAM TP53 mut\u00e9es un b\u00e9n\u00e9fice \u00e0 combiner des BH3 mim\u00e9tiques pour cibler BCL2 et MCL1.<\/p>\n

<\/strong><\/p>\n

Dans nos pratiques<\/strong><\/h3>\n

Le v\u00e9n\u00e9toclax a initialement donn\u00e9 des r\u00e9sultats int\u00e9ressants dans les LAM trait\u00e9es de fa\u00e7on non intensive. Le b\u00e9n\u00e9fice a cependant \u00e9t\u00e9 contrebalanc\u00e9 par l\u2019\u00e9mergence de r\u00e9sistances ou rechutes notamment li\u00e9es aux clones mut\u00e9s TP53. Ces r\u00e9sultats montrent qu\u2019il serait possible de restaurer l\u2019efficacit\u00e9 du v\u00e9n\u00e9toclax en ciblant d\u2019autres mol\u00e9cules des voies d\u2019apoptose et en combinant diff\u00e9rentes drogues.<\/p>\n<\/p>\n

Le regard du statisticien<\/strong><\/h3>\n

La publication propose une panoplie de graphiques pour appuyer leur d\u00e9monstration (donn\u00e9es de cytom\u00e9trie en flux, \u00e9volution cellulaires, viabilit\u00e9, etc.), ainsi que des courbes de Kaplan-Meier portant sur quelques individus. Il se pose toujours la question pour des biostatisticiens d\u2019illustrer graphiquement des statistiques telles que des moyennes et \u00e9cart-types sur si peu d\u2019\u00e9chantillons (une habitude certes, mais pas forc\u00e9ment une bonne).<\/p>\n

<\/strong><\/p>\n

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