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International audience; Contexte scientifique: Malgré des avancées majeures en oncologie depuis vingt ans, 20 % des enfants et adolescents atteints d'un cancer en France décèdent de leur maladie et parmi ceux qui survivent, beaucoup gardent pendant toute leur vie des séquelles plus ou moins invalidantes consécutives à leur traitement. C'est pourquoi en 2017, les chercheurs, cliniciens, biologistes et étudiants français travaillant dans le domaine de la recherche fondamentale et translationnelle en oncologie pédiatrique se sont organisés en réseau sous le nom de REACT4KIDS (https:// react4kids.apps-dev.io/). Ce réseau a pour objectif principal de mieux coordonner les efforts des équipes de recherche françaises (une trentaine) travaillant sur les cancers de l'enfant afin de faire émerger de nouvelles pistes thérapeutiques. Chaque année, REACT4KIDS organise un colloque afin que ces équipes puissent se rencontrer, présenter leurs travaux, partager leurs données et mettre en place de nouvelles collaborations. Cette année, ce colloque scientifique était également tourné vers l'international, avec la venue de deux conférenciers étrangers de renommée mondiale, et vers la société, avec la participation de nombreuses associations de patients et le grand public. Après la tenue des deux premiers colloques en oncologie pédiatrique au centre Léon-Bérard à Lyon, la ville de Bordeaux a été choisie pour organiser la 3 e édition de cette manifestation.

International audience; Tyrosine kinase inhibitors (TKI) constitute the frontline treatment for chronic myeloid leukemia patients. Dasatinib, a second-generation TKI, was developed to overcome TKI resistances. However, dasatinib resistances are also described but remain less characterized. To mimic in vivo acquired dasatinib resistance, the BCR-ABL1-positive cell line K562 was transiently treated with a pharmacological concentration of dasatinib, for a short time in the presence of stem cell factor. A dasatinib resistant counterpart (K562 RES) was developed. Investigation of resistance mechanisms using kinase substrate arrays revealed that FYN was overactivated in K562 RES. The FYN inhibitor KX2-391 cooperated with dasatinib to block K562 RES proliferation. Cell tracking experiments showed that activated FYN support cell proliferation independently of BCR-ABL1 in K562 RES cells. Moreover, the MEK-ERK pathway was found hyper-phosphorylated in K562 RES cells even in the presence of dasatinib. Actually, ERK1/2 activity supported viability in K562 RES only in the absence of BCR-ABL1 activity. Finally, BCR-ABL1 and MEK inhibitor combination was sufficient to induce cell death even in non-proliferating resistant cells. Considering the conditions used to generate this dasatinib resistant cell line, such a resistance mechanism could be found in dasatinib treated patients. Consequently, it is valuable to know that inhibition of the MEK-ERK1/2 axis can overcome this resistance.

International audience; We have sequenced the ura5 gene of the filamentous fungus Podospora anserina. The deduced sequence for the orotidylic acid pyrophosphorylase (OMPppase) has been compared with the Escherichia coli enzyme which is the only known sequence for this enzyme. This comparison shows extensive blocks of homology. The expression of the ura5 gene has been studied in a ura5 mutant which has been transformed by a recombinant plasmid carrying the ura5 gene. We observed that strains carrying integrated multicopies of the transforming vector exhibit higher specific activity for OMPppase than wild type (wt). By recombination we have constructed a strain in which the level of this enzyme is 32 times higher than in the wt strain.