* Hematopoietic expression of a chimeric murine-human CALR oncoprotein allows the assessment of anti-CALR antibody immunotherapies in vivo.
- Myeloproliferative neoplasms (MPNs) are characterized by a pathologic expansion of myeloid lineages. Mutations in JAK2, CALR and MPL genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN. We generated a transgenic murine model with conditional expression of the human mutant exon 9 (del52) from the murine endogenous Calr locus. These mice develop essential thrombocythemia like phenotype with marked thrombocytosis and megakaryocytosis. The disease exacerbates with age showing prominent signs of splenomegaly and anemia. The disease is transplantable and mutCALR stem cells show proliferative advantage when compared to wild type stem cells. Transcriptome profiling of hematopoietic stem cells revealed oncogenic and inflammatory gene expression signatures. To demonstrate the applicability of the transgenic animals for immunotherapy, we treated mice with monoclonal antibody raised against the human mutCALR. The antibody treatment lowered platelet and stem cell counts in mutant mice. Secretion of mutCALR did not constitute a significant antibody sink. This animal model not only recapitulates human MPN but also serves as a relevant model for testing immunotherapeutic strategies targeting epitopes of the human mutCALR.
=>表現すること, 式, 表現, 表示, 言い回し, 表現法, 表情
Overview of noun expression
The noun expression has 9 senses (first 6 from tagged texts)
1. (23) expression, look, aspect, facial expression, face -- (the feelings expressed on a person's
face; "a sad expression"; "a look of triumph"; "an angry face")
2. (18) expression, manifestation, reflection, reflexion -- (expression without words; "tears are an
expression of grief"; "the pulse is a reflection of the heart's condition")
3. (15) expression, verbal expression, verbalism -- (the communication (in speech or writing) of
your beliefs or opinions; "expressions of good will"; "he helped me find verbal expression for my
ideas"; "the idea was immediate but the verbalism took hours")
4. (5) saying, expression, locution -- (a word or phrase that particular people use in particular
situations; "pardon the expression")
5. (4) formulation, expression -- (the style of expressing yourself; "he suggested a better
formulation"; "his manner of expression showed how much he cared")
6. (4) formula, expression -- (a group of symbols that make a mathematical statement)
7. expression -- ((genetics) the process of expressing a gene)
8. construction, grammatical construction, expression -- (a group of words that form a constituent
of a sentence and are considered as a single unit; "I concluded from his awkward constructions that
he was a foreigner")
9. expression -- (the act of forcing something out by squeezing or pressing; "the expression of milk
from her breast")
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