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Influence of BM niches on leukemic B cells in PAX5-ELN mice

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.

ORGANISM(S): Mus musculus

PROVIDER: GSE297080 | GEO | 2026/05/26

REPOSITORIES: GEO

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Influence of BM niches on pre-leukemic B cells in PAX5-ELN mice

Project description: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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