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Updated: May 25, 2026
Identifying Bone Marrow Microenvironmental Populations in Myelodysplastic Syndrome and Acute Myeloid Leukemia
Published on: November 10, 2023
Signals from the bone marrow B cell niches shape pre-leukemic fate in a murine model of B cell acute lymphoblastic
Marjorie C Delahaye1,2, Simon Léonard2, Jeoffrey Pelletier1
1Aix Marseille University, CNRS, INSERM, Institut Paoli Calmettes, CRCM, Marseille, France.
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 demonstrate that signals from bone marrow (BM) niches trigger leukemogenesis in cooperation with driver mutations and determine the fate of pre-leukemic B cells.
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 demonstrate that signals from bone marrow (BM) niches trigger leukemogenesis in cooperation with driver mutations and determine the fate of pre-leukemic B cells.
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