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Article Dans Une Revue Leukemia Research Année : 2022

Hypoxia regulates CD9 expression and dissemination of B lymphoblasts

Arnaud Villacreces

Résumé

Acute lymphoblastic leukemias (ALL) are the most frequent cancer in children and derive most often from B-cell precursors. Current survival rates roughly reach 90% at 10 years from diagnosis. However, 15-20% of children still relapse with a significant risk of death. Our previous work showed that the transmembrane protein CD9 plays a major role in lymphoblasts migration into sanctuary sites, especially in testis, through the activation of RAC1 signaling upon blasts stimulation with C-X-C chemokine ligand 12 (CXCL12). Here, we identified common factors shared by the bone marrow and extramedullary niches which could upregulate CD9 expression and function. We found that low oxygen levels enhance CD9 expression both at mRNA and protein levels. We further determined that Hypoxia Inducible Factor 1 alpha (HIF1 alpha), the master transcription factor involved in hypoxia response, binds directly CD9 promoter and induce CD9 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 HIF1 alpha signaling pathway promotes ALL cells engraftment in a CD9-dependent manner. The present work increments our understanding of CD9 implication in ALL pathogenesis.
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Licence : CC BY NC - Paternité - Pas d'utilisation commerciale

Dates et versions

hal-03888260 , version 1 (28-02-2023)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

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Jérémie Rouger-Gaudichon, Elie Cousin, Helene Jakobczyk, Lydie Debaize, Anne-Gäelle Rio, et al.. Hypoxia regulates CD9 expression and dissemination of B lymphoblasts. Leukemia Research, 2022, 123, pp.106964. ⟨10.1016/j.leukres.2022.106964⟩. ⟨hal-03888260⟩
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