{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:28:44Z","timestamp":1785792524834,"version":"3.56.0"},"reference-count":81,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significance: Tyrosine kinase inhibitors (TKIs) have transformed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) into a largely manageable chronic disease. However, off-target toxicities are increasingly recognized; rarer complications such as bone marrow edema (BME) remain underreported. BME is a radiological syndrome characterized by excess intramedullary fluid on fat-suppressed T2\/STIR magnetic resonance imaging sequences and may progress to irreversible osteochondral damage if unrecognized. We report a case series of TKI-associated BME and propose a practical diagnostic-therapeutic framework. Case Presentation: We describe three patients with Ph+ CML who developed acute, MRI-confirmed BME of the lower limb during TKI therapy. Case 1 developed unilateral then bilateral knee BME, temporally associated first with dasatinib and subsequently with imatinib; symptoms improved after TKI interruption, bisphosphonate therapy, and supportive measures, and did not recur after switching to bosutinib. Case 2 presented with proximal femoral BME during long-term imatinib; imatinib was stopped, intravenous neridronate administered, and bosutinib initiated with clinical recovery and later near-complete radiological resolution. Case 3 experienced multifocal foot and ankle BME during imatinib; symptoms resolved after drug discontinuation and bisphosphonate therapy, and disease control was re-established with bosutinib without recurrence of BME. All patients underwent molecular monitoring and mutational analysis to guide safe therapeutic switching. Discussion: Temporal association across cases and the differential kinase profiles of implicated drugs suggest PDGFR (and to a lesser extent, c-KIT) inhibition as a plausible mechanistic driver of TKI-associated BME. PDGFR-\u03b2 blockade may impair pericyte-mediated microvascular integrity, increase interstitial fluid extravasation, and alter osteoblast\/osteoclast coupling, promoting intramedullary edema. Management combining MRI confirmation, temporary TKI suspension, bone-directed therapy (bisphosphonates, vitamin D\/calcium), symptomatic care, and, when required, therapeutic switching to a PDGFR-sparing agent (bosutinib) led to clinical recovery and preservation of leukemia control in our series. Conclusions: BME is an underrecognized, potentially disabling, TKI-related adverse event in CML. Prompt recognition with targeted MRI and a multidisciplinary, stepwise approach that includes temporary TKI adjustment, bone-directed therapy, and consideration of PDGFR-sparing alternatives can mitigate morbidity while maintaining disease control. Prospective studies are needed to define incidence, risk factors, optimal prevention, and management strategies.<\/jats:p>","DOI":"10.3390\/diagnostics15243112","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"3112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bone Marrow Edema and Tyrosine Kinase Inhibitors Treatment in Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"15","author":[{"given":"Sabina","family":"Russo","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-2640","authenticated-orcid":false,"given":"Manlio","family":"Fazio","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mirabile","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Sciaccotta","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-158X","authenticated-orcid":false,"given":"Fabio","family":"Stagno","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-8239","authenticated-orcid":false,"given":"Alessandro","family":"Allegra","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/s41375-025-02664-w","article-title":"European LeukemiaNet Recommendations for the Management of Chronic Myeloid Leukemia","volume":"39","author":"Apperley","year":"2025","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/leu.2016.104","article-title":"European LeukemiaNet Recommendations for the Management and Avoidance of Adverse Events of Treatment in Chronic Myeloid Leukaemia","volume":"30","author":"Steegmann","year":"2016","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/ajh.27443","article-title":"Chronic Myeloid Leukemia: 2025 Update on Diagnosis, Therapy, and Monitoring","volume":"99","author":"Jabbour","year":"2024","journal-title":"Am. 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