Hematology · 3 h ago
CALR-mutant MPNs show increased NK-cell TIGIT expression
A translational study examined NK-cell features in a mutant CALR mouse model and in patients with myeloproliferative neoplasms (MPNs). CALR-mutant patient NK cells had higher TIGIT expression than JAK2-mutant patient cells, while TIGIT blockade reduced platelet numbers in a mouse transplant model.
- CALR-mutant patient NK cells showed higher TIGIT expression.
- NK-cell degranulation was preserved in CALR-mutant patients.
- TIGIT blockade reduced platelets in a mouse transplant model.
- Clinical benefit of TIGIT blockade remains untested.
Researchers investigated natural killer (NK) cells in CALR-mutant MPNs, comparing findings from a mouse model with patient samples. The patient analysis included 20 adults with MPN; the article also used a previously published dataset to assess infection patterns by driver mutation. Laboratory endpoints included NK-cell maturation, degranulation and expression of the checkpoint TIGIT, as well as expression of its ligand CD112 on CD34-positive cells.
In the mouse model, NK-cell maturation was unchanged, while blood NK-cell frequency and degranulation were increased. In patients not receiving ruxolitinib, CALR-mutant NK cells retained degranulation ability, exceeding that observed in JAK2-mutant patients. TIGIT expression was higher on NK cells from CALR-mutant, but not JAK2-mutant, patients; CD34-positive cells from MPN patients also showed elevated CD112. In the mouse transplant model, TIGIT-blocking antibody treatment reduced platelet numbers. A separate analysis found higher odds of viral infection in CALR- versus JAK2-mutant patients (odds ratio 2.00; 95% credible interval 1.09–3.54).
The findings support further study of TIGIT blockade in CALR-mutant MPN, but do not establish clinical benefit. The therapeutic result comes from a mouse model, and the patient sample was small; the infection analysis used previously published data.
In practice
For patients with CALR-mutant MPN, the study identifies increased TIGIT expression on NK cells and preserved degranulation compared with findings in JAK2-mutant disease, suggesting a possible immune-checkpoint target for future research. TIGIT blockade reduced platelet numbers only in a mouse transplant model; no patient treatment outcomes or clinical efficacy data are reported. The human patient cohort comprised 20 adults, so these findings do not support changing treatment in practice.
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Leukemia: Mutant calreticulin-driven myeloproliferative neoplasms favour the emergence of TIGIT-positive NK cells ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.