1. Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation
- Author
-
Pelletier, Jeoffrey, Balzano, Marielle, Destin, Jérôme, Montersino, Camille, Delahaye, Marjorie C., Marchand, Tony, Bailly, Anne-Laure, Bardin, Florence, Coppin, Emilie, Goubard, Armelle, Castellano, Remy, de Bruijn, Marjolein J.W., Rip, Jasper, Collette, Yves, Dubreuil, Patrice, Tarte, Karin, Broccardo, Cyril, Hendriks, Rudi W., Schiff, Claudine, Vey, Norbert, Aurrand-Lions, Michel, Mancini, Stéphane J.C., Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was partly supported by grants from the SIRIC (Inca-Inserm-DGOS 6038), the ARC Foundation (PJA#20131200298 and PJA#20161204555 to S.J.C.M., PJA#20141201990 to M.A.-L.), the Ligue Nationale Contre le Cancer (#ELN2020), the ADHO association and the Dutch Cancer Society (KWF Grant 2014–6564 to R.W.H.). J.P. was the recipient of PhD grants from the Région PACA/Inserm/Innate Pharma and from La Ligue Nationale contre le Cancer (#TDCU19117), M.B. from FRM (#FDT20150532380) and M.C.D. from la Ligue Nationale contre le Cancer (IP/SC-16060)., Pulmonary Medicine, and Immunology
- Subjects
Biological sciences ,Cell biology ,Multidisciplinary ,Molecular biology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Article - Abstract
International audience; B-cell acute lymphoblastic leukemia (B-ALL) reflects the malignant counterpart of developing B cells in the bone marrow (BM). Despite tremendous progress in B-ALL treatment, the overall survival of adults at diagnosis and patients at all ages after relapse remains poor. Galectin-1 (GAL1) expressed by BM supportive niches delivers proliferation signals to normal pre-B cells through interaction with the pre-B cell receptor (pre-BCR). Here, we asked whether GAL1 gives non-cell autonomous signals to pre-BCR+ pre-B ALL, in addition to cell-autonomous signals linked to genetic alterations. In syngeneic and patient-derived xenograft (PDX) murine models, murine and human pre-B ALL development is influenced by GAL1 produced by BM niches through pre-BCR-dependent signals, similarly to normal pre-B cells. Furthermore, targeting pre-BCR signaling together with cell-autonomous oncogenic pathways in pre-B ALL PDX improved treatment response. Our results show that non-cell autonomous signals transmitted by BM niches represent promising targets to improve B-ALL patient survival.
- Published
- 2023