NK cells control the progression of myelodysplastic syndrome but become initial disease target in NUP98-HOXD13 mouse model
Telliam Dushime, G.; Ciesla, M.; Lilljebjorn, H.; Ungerback, J.; Yuan, O.; Vo, D. N.; Kotova, O.; Fioretos, T.; Bryder, D.; Bellodi, C.; Sitnicka, E.
Show abstract
Studies in NUP98/HOXD13 mouse model (NHD13tg), progressing from myelodysplastic syndrome (MDS) to different forms of leukemia, demonstrated that T cells had a limited anti-leukemia effect, suggesting the involvement of other immune cells. Natural killer (NK) cells control viral infection and cancer. In MDS and acute myeloid leukemia (AML), patients often acquire disease-induced NK cell dysfunctions. Here, we report that NK cells from NHD13tg mice were reduced before the MDS-onset and specific NK cell depletion accelerated the disease progression and severity. NK cells from NHD13tg mice showed perturbed differentiation and impaired IL-15/IL-2 responses. These defects were cell-intrinsic and mainly affected the KLRG1+ mature NK cells. The expression of Nfil3, Klf2 and Id2 genes, crucial for NK cell development, homeostasis and IL-15 responsiveness, was altered in immature NK cells from NHD13tg mice. Interestingly, these genes were changed in MDS and AML bone marrow patient-samples compared to healthy donors. Our findings highlight a critical role for NK cells in controlling MDS progression and identify new genetic markers for MDS and AML.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency 96%
- Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development 95%
- The miR-15a/16-1 and miR-15b/16-2 clusters regulate early B cell development by limiting IL-7 receptor expression 94%
Similar papers in this journal
- The transcription factor RUNX2 drives the generation of human NK cells and promotes tissue residency 96%
- Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A- NK cells 96%
- Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation 95%
Similar papers in this journal
- EOMES and IL-10 regulate anti-tumor activity of PD-1+ CD4+ T-cells in B-cell Non-Hodgkin lymphoma 96%
- Daratumumab induces mechanisms of immune activation through CD38+ NK cell targeting 95%
- Srsf2P95H/+ co-operates with loss of TET2 to promote myeloid bias and initiate a chronic myelomonocytic leukemia like disease in mice. 95%
Similar papers in this journal
"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.