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

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Pelletier, Jeoffrey | Balzano, Marielle | Destin, Jérôme | Montersino, Camille | Delahaye, Marjorie | 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 | Schiff, Claudine | Vey, Norbert | Aurrand-Lions, Michel | Mancini, Stéphane J.C.

Edité par CCSD ; Elsevier -

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.

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