{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:45:14Z","timestamp":1793371514451,"version":"4.5.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>FLT3<\/jats:italic>\n                      gene mutations, particularly internal tandem duplications (\n                      <jats:italic>FLT3<\/jats:italic>\n                      -ITD), are present in approximately 25%\u201330% of patients with acute myeloid leukemia (AML) and are important drivers of leukemogenesis; less frequently,\n                      <jats:italic>FLT3<\/jats:italic>\n                      mutations occur as tyrosine kinase domain (TKD) variants. Non-canonical variants, such as juxtamembrane domain (JMD) in-frame insertions, are rare and their pathogenic mechanisms and therapeutic sensitivities are less defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case description<\/jats:title>\n                    <jats:p>\n                      We report a 13-year-old female patient with refractory AML harboring a novel in-frame insertion in the\n                      <jats:italic>FLT3<\/jats:italic>\n                      JMD NC_000013.11(NM_004119.3):c.1780_1781insGGGTCCCTCCGCCTACCC; p.(Phe594delinsTrpValProProProThrLeu) identified by next-generation sequencing (NGS). The disease was resistant to standard intensive chemotherapy but showed marked sensitivity to the\n                      <jats:italic>FLT3<\/jats:italic>\n                      inhibitor sorafenib. Following relapse upon sorafenib discontinuation due to cardiac toxicity, the patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) while in active disease (M3 marrow). A sequential myeloablative conditioning regimen consisting of melphalan, fludarabine, and fractionated total body irradiation (TBI-8 Gray) was employed. Post-transplant, sorafenib maintenance was resumed for 2 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>The patient achieved sustained complete remission and remains disease-free 63 months post-HSCT, despite significant pre-transplant comorbidities including fungal pneumonia and a pulmonary artery pseudo-aneurysm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case suggests that non-canonical\n                      <jats:italic>FLT3<\/jats:italic>\n                      JMD insertions may be actionable molecular alterations and highlights the need for further investigation of\n                      <jats:italic>FLT3<\/jats:italic>\n                      inhibitor efficacy and the therapeutic relevance of these rare mutations in AML.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1852452","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:27:06Z","timestamp":1790310426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel juxtamembrane FLT3 in-frame insertion in a child with refractory AML: a case report of durable remission following allogeneic HSCT and FLT3 inhibitor therapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Abdul Ali","family":"Peer-Zada","sequence":"first","affiliation":[{"name":"Molecular Genetics Section, Pathology and Clinical Laboratory Medicine Administration, King Fahad Medical City","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al-Rimawi","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Malaeb","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, King Fahad Medical City","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Faquih","sequence":"additional","affiliation":[{"name":"Computational Sciences Department, Genomic Medicine Centre of Excellence, King Faisal Specialist Hospital and Research Center","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monther","family":"Alhamdoosh","sequence":"additional","affiliation":[{"name":"Computational Sciences Department, Genomic Medicine Centre of Excellence, King Faisal Specialist Hospital and Research Center","place":["Riyadh, Saudi 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