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.
Show 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.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Leukemic stem cells hijack lineage inappropriate signalling pathways to promote their growth 97%
- Role of Stem-Like Cells in Chemotherapy Resistance and Relapse in pediatric T Cell Acute Lymphoblastic Leukemia 97%
- B1 and B2 B cells are characterized by distinct CpG modification states at DNMT3A-maintained enhancers 96%
Similar papers in this journal
- AML/T cell interactomics uncover correlates of patient outcomes and the key role of ICAM1 in T cell killing of AML 96%
- Mutant SETBP1 enhances NRAS-driven MAPK pathway activation to promote aggressive leukemia 96%
- Critical roles of Ikaros and HDAC1 in regulation of heterochromatin and tumor suppression in T-cell acute lymphoblastic leukemia 96%
Similar papers in this journal
- Lymphoid origin of a lineage of intrinsically activated plasmacytoid dendritic cell in mice and humans 96%
- Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin-beta receptor signaling 95%
- Convergent Epigenetic Evolution Drives Relapse in Acute Myeloid Leukemia 95%
Similar papers in this journal
- Defective ribosome assembly impairs leukemia stem cell function in a murine model of acute myeloid leukemia 97%
- Inhibition of mutant IDH1 promotes cycling of acute myeloid leukemia stem cells 96%
- A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.