{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:14:08Z","timestamp":1790615648774,"version":"4.1.0"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006458","name":"Children's Hospital of Philadelphia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["TL1TR001880"],"award-info":[{"award-number":["TL1TR001880"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2020,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly primarily affecting the mediastinum with high mortality rate. We present a patient with KLA and significant disease burden harboring a somatic point mutation in the\n                    <jats:italic>Casitas B lineage lymphoma<\/jats:italic>\n                    (\n                    <jats:italic>CBL<\/jats:italic>\n                    ) gene. She was treated with MEK inhibition with complete resolution of symptoms, near\u2010complete resolution of lymphatic fluid burden, and remodeling of her lymphatic system. While patients with KLA have been reported to harbor mutations in\n                    <jats:italic>NRAS<\/jats:italic>\n                    , here we report for the first time a causative mutation in the\n                    <jats:italic>CBL<\/jats:italic>\n                    gene in a patient with KLA, successfully treated with Ras pathway inhibition.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202012324","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T08:50:31Z","timestamp":1601974231000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Kaposiform lymphangiomatosis effectively treated with MEK inhibition"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8001-5960","authenticated-orcid":false,"given":"Jessica B","family":"Foster","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E","family":"March","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Sheppard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Dori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,7]]},"reference":[{"key":"BFEMMM202012324_CR1","doi-asserted-by":"crossref","first-page":"e20153257","DOI":"10.1542\/peds.2015-3257","volume":"137","author":"DM Adams","year":"2016","unstructured":"Adams DM, Trenor CC 3rd, Hammill AM, Vinks AA, Patel MN, Chaudry G, Wentzel MS, Mobberley\u2010Schuman PS, Campbell LM, Brookbank C et\u00a0al (2016) Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics 137: e20153257","journal-title":"Pediatrics"},{"key":"BFEMMM202012324_CR2","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1038\/s41436-018-0390-0","volume":"21","author":"SF Barclay","year":"2019","unstructured":"Barclay SF, Inman KW, Luks VL, McIntyre JB, Al\u2010Ibraheemi A, Church AJ, Perez\u2010Atayde AR, Mangray S, Jeng M, Kreimer SR et\u00a0al (2019) A somatic activating NRAS variant associated with kaposiform lymphangiomatosis. Genet Med 21: 1517\u20131524","journal-title":"Genet Med"},{"key":"BFEMMM202012324_CR3","doi-asserted-by":"crossref","first-page":"e27790","DOI":"10.1002\/pbc.27790","volume":"66","author":"E Boscolo","year":"2019","unstructured":"Boscolo E, Pastura P, Glaser K, Goines J, Hammill AM, Adams DM, Dickie P, Hsi Dickie B, Le Cras TD (2019) Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis. Pediatr Blood Cancer 66: e27790","journal-title":"Pediatr Blood Cancer"},{"key":"BFEMMM202012324_CR4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jpeds.2013.10.013","volume":"164","author":"SE Croteau","year":"2014","unstructured":"Croteau SE, Kozakewich HP, Perez\u2010Atayde AR, Fishman SJ, Alomari AI, Chaudry G, Mulliken JB, Trenor CC 3rd (2014) Kaposiform lymphangiomatosis: a distinct aggressive lymphatic anomaly. J Pediatr 164: 383\u2013388","journal-title":"J Pediatr"},{"key":"BFEMMM202012324_CR5","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/pbc.23124","volume":"57","author":"AM Hammill","year":"2011","unstructured":"Hammill AM, Wentzel M, Gupta A, Nelson S, Lucky A, Elluru R, Dasgupta R, Azizkhan RG, Adams DM (2011) Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 57: 1018\u20131024","journal-title":"Pediatr Blood Cancer"},{"key":"BFEMMM202012324_CR6","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41591-019-0479-2","volume":"25","author":"D Li","year":"2019","unstructured":"Li D, March ME, Gutierrez\u2010Uzquiza A, Kao C, Seiler C, Pinto E, Matsuoka LS, Battig MR, Bhoj EJ, Wenger TL et\u00a0al (2019) ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor. Nat Med 25: 1116\u20131122","journal-title":"Nat Med"},{"key":"BFEMMM202012324_CR7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s13023-019-1191-5","volume":"14","author":"M Ozeki","year":"2019","unstructured":"Ozeki M, Aoki Y, Nozawa A, Yasue S, Endo S, Hori Y, Matsuoka K, Niihori T, Funayama R, Shirota M et\u00a0al (2019) Detection of NRAS mutation in cell\u2010free DNA biological fluids from patients with kaposiform lymphangiomatosis. Orphanet J Rare Dis 14: 215","journal-title":"Orphanet J Rare Dis"},{"key":"BFEMMM202012324_CR8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1513\/AnnalsATS.201308-287BC","volume":"11","author":"F Safi","year":"2014","unstructured":"Safi F, Gupta A, Adams D, Anandan V, McCormack FX, Assaly R (2014) Kaposiform lymphangiomatosis, a newly characterized vascular anomaly presenting with hemoptysis in an adult woman. Ann Am Thorac Soc 11: 92\u201395","journal-title":"Ann Am Thorac Soc"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202012324.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/emmm.202012324","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/emmm.202012324\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/emmm.202012324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/emmm.202012324.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:30:14Z","timestamp":1779085814000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/emmm.202012324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,7]]},"references-count":8,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10,7]]}},"alternative-id":["BFEMMM202012324"],"URL":"https:\/\/doi.org\/10.15252\/emmm.202012324","relation":{},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,7]]},"assertion":[{"value":"11 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"H.H. is a scientific advisor to Aevi Genomic Medicine Inc., and he and CHOP own shares in the company. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMMM202012324"}}