Matches in SemOpenAlex for { <https://semopenalex.org/work/W4229005067> ?p ?o ?g. }
- W4229005067 endingPage "648" @default.
- W4229005067 startingPage "637" @default.
- W4229005067 abstract "Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is characterized by clonal expansion of natural killer (NK) cells where the underlying genetic mechanisms are incompletely understood. In the present study, we report somatic mutations in the chemokine gene CCL22 as the hallmark of a distinct subset of CLPD-NK. CCL22 mutations were enriched at highly conserved residues, mutually exclusive of STAT3 mutations and associated with gene expression programs that resembled normal CD16dim/CD56bright NK cells. Mechanistically, the mutations resulted in ligand-biased chemokine receptor signaling, with decreased internalization of the G-protein-coupled receptor (GPCR) for CCL22, CCR4, via impaired β-arrestin recruitment. This resulted in increased cell chemotaxis in vitro, bidirectional crosstalk with the hematopoietic microenvironment and enhanced NK cell proliferation in vivo in transgenic human IL-15 mice. Somatic CCL22 mutations illustrate a unique mechanism of tumor formation in which gain-of-function chemokine mutations promote tumorigenesis by biased GPCR signaling and dysregulation of microenvironmental crosstalk. Genomic and transcriptomic analyses of chronic lymphoproliferative disorder of natural killer cells identifies somatic gain-of-function mutations in the chemokine gene CCL22 with cell-extrinsic effects. Mutations caused biased signaling downstream of the G-protein-coupled receptor for CCL22 and deregulated interactions with the hematopoietic microenvironment." @default.
- W4229005067 created "2022-05-08" @default.
- W4229005067 creator A5000319514 @default.
- W4229005067 creator A5001225748 @default.
- W4229005067 creator A5001853627 @default.
- W4229005067 creator A5002989232 @default.
- W4229005067 creator A5005724506 @default.
- W4229005067 creator A5005929047 @default.
- W4229005067 creator A5006718448 @default.
- W4229005067 creator A5018214540 @default.
- W4229005067 creator A5018443231 @default.
- W4229005067 creator A5020527564 @default.
- W4229005067 creator A5021480569 @default.
- W4229005067 creator A5033248637 @default.
- W4229005067 creator A5034572373 @default.
- W4229005067 creator A5035051206 @default.
- W4229005067 creator A5041448618 @default.
- W4229005067 creator A5042015932 @default.
- W4229005067 creator A5043414993 @default.
- W4229005067 creator A5048388170 @default.
- W4229005067 creator A5048744038 @default.
- W4229005067 creator A5050154369 @default.
- W4229005067 creator A5050295936 @default.
- W4229005067 creator A5057272369 @default.
- W4229005067 creator A5060457186 @default.
- W4229005067 creator A5064095780 @default.
- W4229005067 creator A5070945766 @default.
- W4229005067 creator A5071122093 @default.
- W4229005067 creator A5075451106 @default.
- W4229005067 creator A5079511754 @default.
- W4229005067 creator A5082046547 @default.
- W4229005067 date "2022-05-01" @default.
- W4229005067 modified "2023-10-17" @default.
- W4229005067 title "CCL22 mutations drive natural killer cell lymphoproliferative disease by deregulating microenvironmental crosstalk" @default.
- W4229005067 cites W1094448410 @default.
- W4229005067 cites W1554415411 @default.
- W4229005067 cites W1561070512 @default.
- W4229005067 cites W1865508955 @default.
- W4229005067 cites W1965582988 @default.
- W4229005067 cites W1968321644 @default.
- W4229005067 cites W1979207587 @default.
- W4229005067 cites W1980016709 @default.
- W4229005067 cites W1992576863 @default.
- W4229005067 cites W1997849135 @default.
- W4229005067 cites W1998203652 @default.
- W4229005067 cites W2014562478 @default.
- W4229005067 cites W2015784582 @default.
- W4229005067 cites W2020720070 @default.
- W4229005067 cites W2021924499 @default.
- W4229005067 cites W2031901496 @default.
- W4229005067 cites W2034254174 @default.
- W4229005067 cites W2037608249 @default.
- W4229005067 cites W2047598314 @default.
- W4229005067 cites W2067438849 @default.
- W4229005067 cites W2078873071 @default.
- W4229005067 cites W2084293527 @default.
- W4229005067 cites W2086411755 @default.
- W4229005067 cites W2097925286 @default.
- W4229005067 cites W2106512898 @default.
- W4229005067 cites W2108230289 @default.
- W4229005067 cites W2108399722 @default.
- W4229005067 cites W2110579373 @default.
- W4229005067 cites W2122449236 @default.
- W4229005067 cites W2127322768 @default.
- W4229005067 cites W2129741568 @default.
- W4229005067 cites W2130410032 @default.
- W4229005067 cites W2134526812 @default.
- W4229005067 cites W2140845989 @default.
- W4229005067 cites W2145254159 @default.
- W4229005067 cites W2150678612 @default.
- W4229005067 cites W2152526557 @default.
- W4229005067 cites W2153503451 @default.
- W4229005067 cites W2154685907 @default.
- W4229005067 cites W2160536323 @default.
- W4229005067 cites W2162723764 @default.
- W4229005067 cites W2164514428 @default.
- W4229005067 cites W2168397218 @default.
- W4229005067 cites W2169353806 @default.
- W4229005067 cites W2169456326 @default.
- W4229005067 cites W2170136110 @default.
- W4229005067 cites W2179438025 @default.
- W4229005067 cites W2288895418 @default.
- W4229005067 cites W2301758340 @default.
- W4229005067 cites W2310716991 @default.
- W4229005067 cites W2581696375 @default.
- W4229005067 cites W2582527364 @default.
- W4229005067 cites W2713710610 @default.
- W4229005067 cites W2737196618 @default.
- W4229005067 cites W2763346562 @default.
- W4229005067 cites W2765390900 @default.
- W4229005067 cites W2768639020 @default.
- W4229005067 cites W2782408527 @default.
- W4229005067 cites W2799754007 @default.
- W4229005067 cites W2805354679 @default.
- W4229005067 cites W2867868648 @default.
- W4229005067 cites W2887064975 @default.
- W4229005067 cites W2928665623 @default.
- W4229005067 cites W2944125141 @default.