{"entity":{"id":"paper-tiacci-n-engl-j-med","kind":"paper","name":"BRAF mutations in hairy-cell leukemia","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 21663470 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Hairy-cell leukemia (HCL) is a well-defined clinicopathological entity whose underlying genetic lesion is still obscure.\n\nMethods: We searched for HCL-associated mutations by performing massively parallel sequencing of the whole exome of leukemic and matched normal cells purified from the peripheral blood of an index patient with HCL. Findings were validated by Sanger sequencing in 47 additional patients with HCL.\n\nResults: Whole-exome sequencing identified five missense somatic clonal mutations that were confirmed on Sanger sequencing, including a heterozygous mutation in BRAF that results in the BRAF V600E variant protein. Since BRAF V600E is oncogenic in other tumors, further analyses were focused on this genetic lesion. The same BRAF mutation was noted in all the other 47 patients with HCL who were evaluated by means of Sanger sequencing. None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAF V600E variant, including 38 patients with splenic marginal-zone lymphomas or unclassifiable splenic lymphomas or leukemias. In immunohistologic and Western blot studies, HCL cells expressed phosphorylated MEK and ERK (the downstream targets of the BRAF kinase), indicating a constitutive activation of the RAF-MEK-ERK mitogen-activated protein kinase pathway in HCL. In vitro incubation of BRAF-mutated primary leukemic hairy cells from 5 patients with PLX-4720, a specific inhibitor of active BRAF, led to a marked decrease in phosphorylated ERK and MEK. CONCLUSIONS; The BRAF V600E mutation was present in all patients with HCL who were evaluated. This finding may have implications for the pathogenesis, diagnosis, and targeted therapy of HCL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).\n\nIndexed on Europe PMC as PubMed record 21663470 (DOI 10.1056/nejmoa1014209). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/nejmoa1014209"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21663470/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21663470"}],"tags":["europepmc-ingest"],"related":["hairy-cell-leukemia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/nejmoa1014209","pmid":"21663470","authors":"Tiacci E, Trifonov V, Schiavoni G, et al.","paperType":"basic","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-tiacci-n-engl-j-med/","neighbours":{"cancer":[{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","route":"/cancers/hairy-cell-leukemia/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}