| First Author | Isidro-Hernández M | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5159 |
| PubMed ID | 37620322 | Mgi Jnum | J:339291 |
| Mgi Id | MGI:7521348 | Doi | 10.1038/s41467-023-40961-z |
| Citation | Isidro-Hernandez M, et al. (2023) Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice. Nat Commun 14(1):5159 |
| abstractText | The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5(+/-) B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5(+/-)Myd88(+/-) mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5(+/-) mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children. |
