With the increase in survival for children with cancer, part of the focus of current research is aimed towards evaluating how these children are adapting psychosocially. Neurocognitive deficits have been well established. However, there are multiple facets encompassing quality of life, including general mental health, lifestyles and health behaviors, and academic and cognitive functioning. The relationship between neurocognitive and psychosocial functioning has yet to be thoroughly evaluated. The purpose of this study was to investigate the relationship between neurocognitive and psychosocial functioning in survivors of brain tumors and acute lymphoblastic leukemia. Data was collected from existing archival database comprised of patients of the at Cook Children's Medical Center in Texas. The sample consisted of 177 patients between the ages of 3 and 12 who were at least two years post-diagnosis. Measures used included the NEPSY and the Behavioral Assessment for Children. Statistical analyses included a several one-way analysis of variances, an independent samples t-test, a univariate analysis of variance, a hierarchical multiple regression, and odds ratio analyses. Results indicated survivors treated with neurosurgery alone appear to be less at risk for developing behavior problems than other treatment modalities. Also, brain tumor survivors demonstrate more problematic behaviors than survivors of acute lymphoblastic leukemia. Visuospatial functioning, diagnosis, and type of treatment were found to be predictive variables of behavior problems. Attention, and perhaps language, deficits may predispose children to more problems in their behavior. It is concluded that there are other factors affecting behavior in this population that were not accounted for in this analysis. It is recommended for future studies to research the individual clinical scales of the Behavior Assessment System for Children, obtain information from multiple informants, study this relationship longitudinally, and research additional factors that may be influencing the relationship between neurocognitive and psychosocial functioning. This provides evidence of risk factors that should be monitored as the child returns home and to school.

Les leucémies aiguës lymphoblastiques (LAL) sont le cancer le plus fréquent chez l’enfant et dérivent le plus souvent de précurseurs lymphoïdes B. D’importants progrès thérapeutiques ont permis d’améliorer considérablement le pronostic. Néanmoins, 15 à 20 % des enfants rechutent encore. Ces rechutes peuvent survenir de façon isolée ou combinée dans la moelle osseuse, le site primitif des lymphoblastes, et/ou dans des organes extramédullaires tels que le testicule ou le système nerveux central. Notre équipe a montré que la protéine transmembranaire CD9 jouait un rôle majeur dans la migration des blastes dans ces sites et notamment le testicule, par l’activation de la voie RAC1 en réponse à la stimulation des cellules par le CXCL12. Ici, nous avons mis en évidence qu’un faible niveau d’oxygène, caractéristique commune aux niches médullaire et extramédullaires, régulait positivement l’expression de CD9 aux niveaux transcriptionnel et protéique, via la voie majeure de réponse à l’hypoxie, dépendante du facteur de transcription Hypoxia Inducible Factor 1a (HIF1a). Nous montrons que HIF1a se fixe directement sur le promoteur de CD9 pour induire sa transcription. Nous montrons aussi que la protéine CD9 est essentielle aux propriétés d’adhérence et de migration des blastes dans des conditions de basse oxygénation, et que son action pourrait s’exercer à travers RAC1 comme en normoxie. Nos résultats dans des expériences de xénogreffe à des souris indiquent que la voie HIF1a favorise la dissémination des blastes, possiblement à travers la régulation qu’elle exerce sur CD9. Ainsi, ce travail contribue à mieux comprendre le rôle de CD9 dans la pathogenèse des LAL de l’enfant. / Acute lymphoblastic leukemia (ALL) are the most frequent cancer in children and derive most often from B-cell precursors. Huge therapeutic improvements have allowed to reach high survival rates near 90% at 10 years from diagnosis. However, 15-20% of children still relapse with a significant risk of death. Relapses can occur in bone marrow and/or extramedullary sites such as testis or central nervous system, usually referred as “sanctuary sites”. Our previous work showed that the transmembrane protein CD9 plays a major role in lymphoblasts migration into these sites, especially in testis, through the activation of RAC1 signaling upon blasts stimulation with C-X-C chemokine ligand 12 (CXCl12). Here, we addressed the question of putative common factors shared by bone marrow and extramedullary niches which could upregulate CD9 expression and function. Consequently, we found that low oxygen levels could actually enhance CD9 expression both at mRNA and protein levels. We further determined that Hypoxia Inducible Factor 1a (HIF1a), the master transcription factor involved in hypoxia response, binds directly CD9 promoter to induce its transcription. We also showed that CD9 protein is crucial for leukemic cell adhesion and migration at low oxygen levels, possibly through its action on RAC1 signaling. Mouse xenograft experiments indicate that HIF1a signaling pathway favors ALL cells dissemination, which may involve CD9 as well. The present work increments our understanding of CD9 implication in ALL pathogenesis.