{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:38:20Z","timestamp":1791041900922,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Juvenile Myelomonocytic Leukemia (JMML) is a rare and clonal hematopoietic disorder of infancy and early childhood with myeloproliferative\/myelodysplastic features resulting from germline or somatic mutations in the RAS pathway. Treatment is not uniform, with management varying from observation to stem cell transplant. The aim of our retrospective review is to describe the treatment and outcomes of a cohort of patients with JMML or Noonan Syndrome-associated Myeloproliferative Disorder (NS-MPD) to provide management guidance for this rare and heterogeneous disease. We report on 22 patients with JMML or NS-MPD managed at three institutions in the Texas Medical Center. Of patients with known genetic mutations and cytogenetics, 6 harbored germline mutations, 12 had somatic mutations, and 9 showed cytogenetic abnormalities. Overall, 14\/22 patients are alive. Spontaneous clinical remission occurred in one patient with somatic NRAS mutation, as well as two with germline PTPN11 mutations with NS-MPD, and two others with germline PTPN11 mutations and NS-MPD remain under surveillance. Patients with NS-MPD were excluded from treatment analysis as none required chemotherapeutic intervention. All patients (5\/5) treated with 5-azacitidine alone and one of the four treated with 6-mercaptopurine monotherapy had a reduction in mutant variant allele frequency. Transformation to acute myeloid leukemia was seen in two patients who both died. Among patients who received transplants, 7\/13 are alive, and relapse post-transplant occurred in 3\/13 with a median time to relapse of 3.55 months. This report provides insight into therapy responses and long-term outcomes across different genetic subsets of JMML and lends insight into the expected time to spontaneous resolution in patients with NS-MPD with germline PTPN11 mutations.<\/jats:p>","DOI":"10.3390\/cancers16152749","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T13:14:42Z","timestamp":1722604482000},"page":"2749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3338-0244","authenticated-orcid":false,"given":"Bryony J.","family":"Lucas","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Texas Children\u2019s Cancer and Hematology Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy S.","family":"Connors","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Conneely","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Texas Children\u2019s Cancer and Hematology Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Cuglievan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Pediatric Oncology, Children\u2019s Memorial Hermann Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-2267","authenticated-orcid":false,"given":"Miriam B.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Pediatric Oncology, Children\u2019s Memorial Hermann Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-6603","authenticated-orcid":false,"given":"Rachel E.","family":"Rau","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Hospital, University of Washington, Seattle, WA 98105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/sj.leu.2402765","article-title":"A Pediatric Approach to the WHO Classification of Myelodysplastic and Myeloproliferative Diseases","volume":"17","author":"Hasle","year":"2003","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating Morphologic, Clinical, and Genomic Data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4103\/ijc.IJC_694_18","article-title":"Juvenile Myelomonocytic Leukemia: A Case Series of a Rare Hematological Disease","volume":"57","author":"Subramanian","year":"2020","journal-title":"Indian J. 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