PMID- 36335655
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20221227
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Linking)
VI  - 123
DP  - 2022 Dec
TI  - Hypoxia regulates CD9 expression and dissemination of B lymphoblasts.
PG  - 106964
LID - S0145-2126(22)00190-4 [pii]
LID - 10.1016/j.leukres.2022.106964 [doi]
AB  - 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 1alpha (HIF1alpha), 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 HIF1alpha signaling pathway promotes ALL cells 
      engraftment in a CD9-dependent manner. The present work increments our 
      understanding of CD9 implication in ALL pathogenesis.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Rouger-Gaudichon, Jeremie
AU  - Rouger-Gaudichon J
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France; University 
      Hospital, Caen, Department of Pediatric Oncology and Hematology, CHU Caen 
      Normandie, France. Electronic address: rouger-j@chu-caen.fr.
FAU - Cousin, Elie
AU  - Cousin E
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France; University 
      Hospital, Rennes, Pediatric Oncology and Hematology, CHU Rennes, France.
FAU - Jakobczyk, Helene
AU  - Jakobczyk H
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France.
FAU - Debaize, Lydie
AU  - Debaize L
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France.
FAU - Rio, Anne-Gaelle
AU  - Rio AG
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France.
FAU - Forestier, Anne
AU  - Forestier A
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France.
FAU - Arnaud, Marie-Pierre
AU  - Arnaud MP
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France.
FAU - Villacreces, Arnaud
AU  - Villacreces A
AD  - BRIC (BoRdeaux Institute of on Cology), UMR1312, INSERM, Univ. Bordeaux, F-33000, 
      Bordeaux, France.
FAU - Praloran, Vincent
AU  - Praloran V
AD  - Univ. Bordeaux, INSERM, BMGIC, U1035, F33000 Bordeaux, France.
FAU - Jacamo, Rodrigo
AU  - Jacamo R
AD  - Department of Leukemia, Section of Molecular Hematology and Therapy, The 
      University of Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Galibert, Marie-Dominique
AU  - Galibert MD
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France; University 
      Hospital, Rennes, Department of Molecular Genetics and Genomic, CHU Rennes, 
      France.
FAU - Troadec, Marie-Berengere
AU  - Troadec MB
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France; Univ Brest, 
      Inserm, EFS, UMR 1078, GGB, F29200 Brest, France; CHRU Brest, Service de 
      genetique, laboratoire de genetique chromosomique, Brest, France.
FAU - Gandemer, Virginie
AU  - Gandemer V
AD  - Univ Rennes, CNRS, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 
      6290, Equipe Expression des Genes et Oncogenese, Rennes, France; University 
      Hospital, Rennes, Pediatric Oncology and Hematology, CHU Rennes, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220928
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Tetraspanin 29)
RN  - S88TT14065 (Oxygen)
RN  - 0 (CD9 protein, human)
SB  - IM
MH  - Male
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Tetraspanin 29/genetics/metabolism
MH  - Cell Adhesion
MH  - *Signal Transduction
MH  - *Hypoxia
MH  - Oxygen
OTO - NOTNLM
OT  - Acute lymphoblastic leukemia
OT  - CD9
OT  - Children
OT  - Hypoxia
OT  - Tetraspanin
COIS- Conflict of interest The authors declare no conflict of interest. The funders had 
      no role in the design of the study; in the collection, analyses, or 
      interpretation of data; in the writing of the manuscript, or in the decision to 
      publish the results.
EDAT- 2022/11/07 06:00
MHDA- 2022/11/30 06:00
CRDT- 2022/11/06 18:07
PHST- 2022/05/24 00:00 [received]
PHST- 2022/09/21 00:00 [revised]
PHST- 2022/09/26 00:00 [accepted]
PHST- 2022/11/07 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/11/06 18:07 [entrez]
AID - S0145-2126(22)00190-4 [pii]
AID - 10.1016/j.leukres.2022.106964 [doi]
PST - ppublish
SO  - Leuk Res. 2022 Dec;123:106964. doi: 10.1016/j.leukres.2022.106964. Epub 2022 Sep 
      28.