Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Among 103 patients with multidrug-resistant HIV who initiated raltegravir, etravirine, and darunavir/ritonavir-containing regimen in the ANRS 139 TRIO trial, 100 participated in extended follow-up and continued study treatment until week 96. Among them, 87 (87%) received an optimized background therapy including either nucleoside reverse transcriptase inhibitors or enfuvirtide, they were 78 (78%) at week 96. At week 96, 88% achieved durable virologic response (<50 copies/mL). CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass-resistant virus.
ISSN: 1525-4135

hal-00875207
https://hal.archives-ouvertes.fr/hal-00875207
DOI : 10.1097/QAI.0b013e31824bb720
PUBMED : 22293546

Éditeur(s) : HAL CCSD Carnets de Geologie
Résumé : International audience
Des associations d'ostracodes provenant de la région d'Antsiranana, ex Diego-Suarez, dans le N de Madagascar ont été étudiées au niveau systématique. Dans l'intervalle Albien-Turonien moyen, 29 espèces appartenant à 21 genres ont été reconnues, 10 nouvelles espèces, un nouveau genre (Malagasyella) et un nouveau sous-genre (Hemiglenocythere) ont été créés. L'Albien ainsi que le Cénomanien inférieur se caractérisent par des associations bien différenciées. D'un point de vue paléoécologique, la succession des faunes d'ostracodes montre une baisse progressive du niveau de la mer d'un milieu de bassin-talus à l'Albien à un environnement de plate-forme externe au Turonien. Pendant cette période les faunes d'ostracodes de Madagascar montrent de fortes affinités avec celles de l'Inde (Rajasthan) ce qui mène à proposer l'existence de province faunistique indo-malgache.
ISSN: 1765-2553

hal-00386005
https://hal.archives-ouvertes.fr/hal-00386005
https://hal.archives-ouvertes.fr/hal-00386005/document
https://hal.archives-ouvertes.fr/hal-00386005/file/CG2009_A01.pdf