{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:16:51Z","timestamp":1790108211735,"version":"4.0.1"},"reference-count":141,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["PID2020-117645RB-I00"],"award-info":[{"award-number":["PID2020-117645RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["RYC2020-029400-I"],"award-info":[{"award-number":["RYC2020-029400-I"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018779","name":"FERO Foundation","doi-asserted-by":"publisher","award":["BFero2020.03"],"award-info":[{"award-number":["BFero2020.03"]}],"id":[{"id":"10.13039\/501100018779","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of Andorra","award":["ATC025-AND-2020"],"award-info":[{"award-number":["ATC025-AND-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic\/myeloproliferative neoplasm of early childhood. Most of JMML patients experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation, which is currently the only curative treatment. JMML is characterized by RAS signaling hyperactivation, which is mainly driven by mutations in one of five genes of the RAS pathway, including PTPN11, KRAS, NRAS, NF1, and CBL. These driving mutations define different disease subtypes with specific clinico-biological features. Secondary mutations affecting other genes inside and outside the RAS pathway contribute to JMML pathogenesis and are associated with a poorer prognosis. In addition to these genetic alterations, JMML commonly presents aberrant epigenetic profiles that strongly correlate with the clinical outcome of the patients. This observation led to the recent publication of an international JMML stratification consensus, which defines three JMML clinical groups based on DNA methylation status. Although the characterization of the genomic and epigenomic landscapes in JMML has significantly contributed to better understand the molecular mechanisms driving the disease, our knowledge on JMML origin, cell identity, and intratumor and interpatient heterogeneity is still scarce. The application of new single-cell sequencing technologies will be critical to address these questions in the future.<\/jats:p>","DOI":"10.3390\/cancers14051335","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:35:50Z","timestamp":1646598950000},"page":"1335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-1498","authenticated-orcid":false,"given":"Claudia","family":"Fi\u00f1ana","sequence":"first","affiliation":[{"name":"Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain"},{"name":"Immuno Procure, Catalan Institute of Oncology (ICO), 08916 Badalona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3774-3767","authenticated-orcid":false,"given":"Noel","family":"G\u00f3mez-Molina","sequence":"additional","affiliation":[{"name":"Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain"},{"name":"Immuno Procure, Catalan Institute of Oncology (ICO), 08916 Badalona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Alonso-Moreno","sequence":"additional","affiliation":[{"name":"Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain"},{"name":"Immuno Procure, Catalan Institute of Oncology (ICO), 08916 Badalona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7493-7072","authenticated-orcid":false,"given":"Laura","family":"Belver","sequence":"additional","affiliation":[{"name":"Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain"},{"name":"Immuno Procure, Catalan Institute of Oncology (ICO), 08916 Badalona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1182\/blood.V77.5.925.925","article-title":"Selective Hypersensitivity to Granulocyte-Macrophage Colony-Stimulating Factor by Juvenile Chronic Myeloid Leukemia Hematopoietic Progenitors","volume":"77","author":"Emanuel","year":"1991","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1182\/blood-2014-08-550483","article-title":"How I treat juvenile myelomonocytic leukemia","volume":"125","author":"Locatelli","year":"2015","journal-title":"Blood"},{"key":"ref_4","first-page":"3534","article-title":"Chronic Myelomonocytic Leukemia in Childhood: A Retrospective Analysis of 110 Cases","volume":"89","author":"Niemeyer","year":"1997","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s12185-014-1715-7","article-title":"Transplantation for juvenile myelomonocytic leukemia: A retrospective study of 30 children treated with a regimen of busulfan, fludarabine, and melphalan","volume":"101","author":"Yabe","year":"2014","journal-title":"Int. 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