Integrin-deficient T cell leukemia accumulates in the central nervous system
Lux, S. Y.; Chen, C.; Subhan, B. S.; Chung, H.; Okuniewska, M.; Martin, K. A.; Caslin, A. Y.; Schiavo, J. K.; Vernejoul, J. B.; Froemke, R.; Cammer, M.; Schwab, S. R.
Show abstract
T-cell acute lymphoblastic leukemia (T-ALL) spreads aggressively to the central nervous system (CNS), particularly the leptomeninges. Children with T-ALL are treated with high-dose, CNS-directed chemotherapy, which can cause lasting neurotoxicity and is not always effective. Little is known about how T-ALL enters and persists within the CNS. However, normal T cell migration into the CNS has been extensively studied. Two integrins--VLA-4 and LFA-1--mediate normal T cell entry to the CNS, and VLA-4 blockade effectively treats multiple sclerosis by excluding T cells from the brain. We hypothesized that these integrins would likewise be required for T-ALL CNS entry. Unexpectedly, not only were VLA-4 and LFA-1 dispensable for T-ALL to reach the CNS, integrin-deficient T-ALL accumulated in the CNS compared to control. Mechanistically, integrin loss accelerated T-ALL proliferation in the CNS, suggesting that integrin-mediated interactions may promote quiescence in this space. Integrin blockade synergized with chemotherapy targeting proliferating cells, raising the possibility that combination therapy might be a powerful strategy.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia 93%
- Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals 93%
- An engineered CRISPR/Cas9 mouse line for simultaneous readout of lineage histories and gene expression profiles in single cells 93%
Similar papers in this journal
- Integrin signaling is critical for myeloid-mediated support of T-cell acute lymphoblastic leukemia 98%
- Role of Stem-Like Cells in Chemotherapy Resistance and Relapse in pediatric T Cell Acute Lymphoblastic Leukemia 96%
- Cooperative super-enhancer inactivation caused by heterozygous loss of CREBBP and KMT2D skews B cell fate decisions and yields T cell-depleted lymphomas 95%
Similar papers in this journal
Similar papers in this journal
- Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS/AML 94%
- Broad de-regulated U2AF1 splicing is prognostic and augments leukemic transformation via protein arginine methyltransferase activation 94%
- Distinct evolutionary paths in chronic lymphocytic leukemia during resistance to graft-versus-leukemia 94%
"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.