1. Niche-expressed Galectin-1 is involved in pre-B acute lymphoblastic leukemia relapse through pre-B cell receptor activation.
- Author
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Pelletier J, Balzano M, Destin J, Montersino C, Delahaye MC, Marchand T, Bailly AL, Bardin F, Coppin E, Goubard A, Castellano R, de Bruijn MJW, Rip J, Collette Y, Dubreuil P, Tarte K, Broccardo C, Hendriks RW, Schiff C, Vey N, Aurrand-Lions M, and Mancini SJC
- Abstract
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., Competing Interests: The authors declare no competing financial interests., (© 2023 The Author(s).)- Published
- 2023
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