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<p>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.</p><p></p>

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

  • 期刊论文

  • 发表日期：

    2026年5月23日

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  • Marjorie C. Delahaye,
  • Simon Léonard,
  • Jeoffrey Pelletier,
  • Jérôme Destin,
  • Florence Bardin,
  • Mourad Ounis,
  • Céline Monvoisin,
  • Naïs Prade,
  • Laurine Gil,
  • Audrey Dauba,
  • Pierre Milpied,
  • Ahmed Amine Khamlichi,
  • Eric Delabesse,
  • Tony Marchand,
  • Cyril Broccardo,
  • Michel Aurrand-Lions,
  • Bastien Gerby,
  • Stéphane JC Mancini

摘要

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.