{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:16:15Z","timestamp":1792444575865,"version":"4.5.0"},"reference-count":45,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Indolent systemic mastocytosis (ISM) patients have a normal life expectancy, except in the 5% to 10% of cases that progress to more advanced SM (advSM), which has a significantly poorer outcome. Mutations in genes other than KIT frequently found in myeloid neoplasms have been associated with a poorer outcome among advSM, whereas limited information exists about their frequency and prognostic impact in ISM. We investigated the frequency and prognostic impact of variants in 18 genes, found to be altered in advSM, in 322 ISM patients (median follow-up, 5.7 years) divided into discovery (n = 200) and validation (n = 122) cohorts. Overall, 71 genetic variants were detected in 55 of 322 (17%) patients. Mutated ISM cases, particularly those carrying ASXL1, RUNX1, and\/or DNMT3A (A\/R\/D) pathogenic variant allele frequencies (VAFs) \u2265 30%, exhibited significantly shortened (P &amp;lt; .001) progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed that serum \u03b22-microglobulin (s\u03b22M) levels &amp;gt; 2.5 \u00b5g\/mL (hazard ratio [HR], 9.8; P = .001), together with a KIT D816V VAF \u2265 1% in bone marrow (BM) (HR, 10.1; P = .02) and pathogenic variants of A\/R\/D VAFs \u2265 30% (HR, 4.2; P = .02), were the best combination of independent predictors for PFS. In turn, A\/R\/D gene pathogenic VAF \u2265 30% was the only independent predictor for OS (HR, 51.8; P &amp;lt; .001). Based on these variables, 2 scoring systems were constructed for risk stratification of ISM at diagnosis with significantly different 10-year PFS (100%, 91%, 0% for scores of 0, 1, \u22652, respectively) and OS (100% and 50% for scores of 0 and 1) rates.<\/jats:p>","DOI":"10.1182\/blood.2018886507","type":"journal-article","created":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T02:39:03Z","timestamp":1559356743000},"page":"456-468","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":64,"title":["Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis"],"prefix":"10.1182","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8982-5663","authenticated-orcid":false,"given":"Javier I.","family":"Mu\u00f1oz-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Cancer Research Center (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service, NUCLEUS, Universidad de Salamanca, Salamanca, Spain;"},{"name":"Spanish Network on Mastocytosis, Toledo and Salamanca, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain;"},{"name":"Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-4473","authenticated-orcid":false,"given":"Iv\u00e1n","family":"\u00c1lvarez-Twose","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis, Toledo and Salamanca, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain;"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha, Virgen del Valle Hospital, Toledo, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7965-7512","authenticated-orcid":false,"given":"Mar\u00eda","family":"Jara-Acevedo","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis, Toledo and Salamanca, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain;"},{"name":"Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain;"},{"name":"Sequencing Service and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Henriques","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis, Toledo and Salamanca, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain;"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha, Virgen del Valle Hospital, Toledo, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Vi\u00f1as","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis, Toledo and Salamanca, Spain;"},{"name":"Sequencing Service and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8178-9768","authenticated-orcid":false,"given":"Carlos","family":"Prieto","sequence":"additional","affiliation":[{"name":"Bioinformatics Service, NUCLEUS, Universidad de Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"S\u00e1nchez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Spanish Network on Mastocytosis, Toledo and Salamanca, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain;"},{"name":"Instituto de Estudios de Mastocitosis de Castilla La Mancha, Virgen del Valle Hospital, Toledo, Spain; 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