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Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation.

Jeoffrey Pelletier | Marielle Balzano | Jérôme Destin | Camille Montersino | Marjorie C Delahaye | Tony Marchand | Anne-Laure Bailly | Florence Bardin | Emilie Coppin | Armelle Goubard | Remy Castellano | Marjolein J W de Bruijn | Jasper Rip | Yves Collette | Patrice Dubreuil | Karin Tarte | Cyril Broccardo | Rudi W Hendriks | Claudine Schiff | Norbert Vey | Michel Aurrand-Lions | Stéphane J C Mancini
iScience | 2023

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.

Pubmed ID: 37009219 RIS Download

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