Signals from the bone marrow B cell niches shape pre-leukemic fate in murine B cell acute lymphoblastic leukemia

Delahaye, M. C.; Leonard, S.; Pelletier, J.; Destin, J.; Bardin, F.; Ounis, M.; Monvoisin, C.; Prade, N.; Gil, L.; Dauba, A.; Milpied, P.; Khamlichi, A. A.; Delabesse, E.; Marchand, T.; Broccardo, C.; Aurrand-Lions, M.; Gerby, B.; Mancini, S. J.

doi:10.1101/2025.02.14.638228

bioRxiv · 10.1101/2025.02.14.638228

Signals from the bone marrow B cell niches shape pre-leukemic fate in murine B cell acute lymphoblastic leukemia

Delahaye, M. C.·Leonard, S.·Pelletier, J.·Destin, J.·Bardin, F.·Ounis, M.·Monvoisin, C.·Prade, N.·Gil, L.·Dauba, A.·Milpied, P.·Khamlichi, A. A.·Delabesse, E.·Marchand, T.·Broccardo, C.·Aurrand-Lions, M.·Gerby, B.·Mancini, S. J.

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Abstract

The bone marrow (BM) microenvironment plays a key role in supporting B cell development. In acute lymphoblastic leukemia (B-ALL), the acquisition of oncogenic driver mutations blocks B cell differentiation at specific stages. When these pre-leukemic cells acquire secondary mutations, B-ALL develops. However, the role of the BM microenvironment in pre-leukemic cell fate remains unknown. Here, using a murine model of spontaneous B-ALL development, we show that disrupted pre-BCR signaling in pre-leukemic cells modifies their fate. Blocking expression of the pre-BCR ligand Galectin-1 by the microenvironment impaired pre-leukemic cell proliferation and leukemia-initiating capacity. Consequently, B-ALL development was delayed, and B-ALL had a more mature phenotype, with cells expressing a BCR. Secondary mutations were also altered by changes to Galectin-1 expression, in its absence mutations almost exclusively affected IL-7R signaling rather than both pre-BCR and IL-7R signaling. These results show that signals from BM niches can directly influence pre-leukemic B cell fate.

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Delahaye, M. C., Leonard, S., Pelletier, J., Destin, J., Bardin, F., Ounis, M., Monvoisin, C., Prade, N., Gil, L., Dauba, A., Milpied, P., Khamlichi, A. A., Delabesse, E., Marchand, T., Broccardo, C., Aurrand-Lions, M., Gerby, B., Mancini, S. J.. 2025-02-17. Signals from the bone marrow B cell niches shape pre-leukemic fate in murine B cell acute lymphoblastic leukemia. https://doi.org/10.1101/2025.02.14.638228

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