{"id":16389,"date":"2022-12-08T15:26:46","date_gmt":"2022-12-08T14:26:46","guid":{"rendered":"https:\/\/convergences.online\/hemato\/?p=16389"},"modified":"2024-12-11T18:31:14","modified_gmt":"2024-12-11T17:31:14","slug":"emergence-de-mutations-de-tp53-sous-lenalidomide","status":"publish","type":"post","link":"https:\/\/www.hematostat.net\/en\/emergence-de-mutations-de-tp53-sous-lenalidomide\/","title":{"rendered":"\u00c9mergence de mutations de TP53 sous l\u00e9nalidomide"},"content":{"rendered":"

R\u00e9f. : HematoStat.net ; 3 (4) : R64<\/p>\n

Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms.Sperling AS, Guerra VA, Kennedy JA, Yan Y, Hsu JI, Wang F, et al. Blood. 20 oct 2022;140(16):1753\u201163.<\/a><\/i><\/p>\n

R\u00e9sum\u00e9 de l’article<\/h3>\n

Cette \u00e9tude r\u00e9trospective portait sur 416 patients pr\u00e9sentant une h\u00e9mopathie secondaire \u00e0 un traitement (t-NM). Une alt\u00e9ration g\u00e9nique \u00e9tait retrouv\u00e9e chez 85 % des patients en analyse NGS. Les mutations de TP53 (37 %) et PPM1D (19 %) \u00e9taient les plus fr\u00e9quentes. L\u2019exposition pr\u00e9alable aux inhibiteurs du prot\u00e9asome ou aux IMID, et en particulier au l\u00e9nalidomide, \u00e9tait significativement associ\u00e9e \u00e0 la pr\u00e9sence d\u2019une mutation de TP53.<\/p>\n

Dans nos pratiques<\/h3>\n

Les auteurs ont pu r\u00e9pliquer l\u2019effet observ\u00e9 dans un mod\u00e8le murin en montrant que le l\u00e9nalidomide entra\u00eenait sp\u00e9cifiquement un avantage s\u00e9lectif pour les cellules souches avec mutation TPR-53, participant \u00e0 la s\u00e9lection de ces clones. <\/span>La compr\u00e9hension des m\u00e9canismes de s\u00e9lection de mutation d\u2019h\u00e9matopo\u00ef\u00e8se clonale sous l\u2019influence de diff\u00e9rents traitements s\u2019affine et permettra, peut-\u00eatre, d\u2019adapter le traitement pour les patients les plus \u00e0 risque de t-NM.<\/p>\n

Regard du statisticien<\/h3>\n

Hormis le fait qu\u2019il s\u2019agisse d\u2019une \u00e9tude r\u00e9trospective, cette analyse g\u00e9n\u00e9tique a utilis\u00e9 des outils statistiques tr\u00e8s pointus afin d\u2019obtenir des r\u00e9sultats solides. Pour effectuer les r\u00e9gression multivari\u00e9es (avec variables d\u2019ajustement), les auteurs ont utilis\u00e9 par exemple le VIF (Variante Inflation Factor<\/i>) pour \u00e9tudier la multi-colin\u00e9arit\u00e9 des variables, et si besoin une r\u00e9gression logistique de Firth (utile pour la r\u00e9duction des biais lorsque le nombre d\u2019\u00e9v\u00e9nements est faible). Ils ont \u00e9galement pens\u00e9 \u00e0 remplacer les p-values<\/i> par des FDR (false discovery rate<\/i>) dans le cadre de tests multiples. <\/span><\/p>\n<\/div><\/div><\/div><\/div><\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":16390,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_uf_show_specific_survey":0,"_uf_disable_surveys":false,"footnotes":""},"categories":[36],"tags":[354,355,356,357],"ppma_author":[442],"class_list":["post-16389","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-revue-de-presse","tag-firth","tag-lenalidomide","tag-mutation-tpr-53","tag-variante-inflation-factor","author-marion"],"aioseo_notices":[],"authors":[{"term_id":442,"user_id":2,"is_guest":0,"slug":"marion","display_name":"HematoStat.net (M)","avatar_url":{"url":"https:\/\/www.hematostat.net\/wp-content\/uploads\/2024\/01\/favicon-hematoStat.png","url2x":"https:\/\/www.hematostat.net\/wp-content\/uploads\/2024\/01\/favicon-hematoStat.png"},"first_name":"HematoStat.net (M)","last_name":"","user_url":"","description":""}],"_links":{"self":[{"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/posts\/16389","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/comments?post=16389"}],"version-history":[{"count":2,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/posts\/16389\/revisions"}],"predecessor-version":[{"id":18238,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/posts\/16389\/revisions\/18238"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/"}],"wp:attachment":[{"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/media?parent=16389"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/categories?post=16389"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/tags?post=16389"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.hematostat.net\/en\/wp-json\/wp\/v2\/ppma_author?post=16389"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}