{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:10:29Z","timestamp":1792789829878,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Research, Technology and Space","doi-asserted-by":"publisher","award":["01EO2101"],"award-info":[{"award-number":["01EO2101"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"award":["01EO2101"],"award-info":[{"award-number":["01EO2101"]}],"id":[{"id":"https:\/\/ror.org\/04pz7b180","id-type":"ROR","asserted-by":"publisher"}]},{"name":"German Centers for Health Research","award":["2020\/21"],"award-info":[{"award-number":["2020\/21"]}],"id":[{"id":"https:\/\/ror.org\/044wq1q96","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2020\/21"],"award-info":[{"award-number":["2020\/21"]}],"id":[{"id":"https:\/\/ror.org\/044wq1q96","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Myelodysplastic neoplasms (MDSs) are clonal hematopoietic stem cell disorders associated with ineffective hematopoiesis, chronic inflammation, and increased cardiovascular morbidity. Although metabolic dysregulation has been implicated in MDS pathogenesis, systemic metabolic alterations remain incompletely characterized. Methods: Plasma samples from treatment-na\u00efve patients with MDS or chronic myelomonocytic leukemia (CMML) and age-matched healthy controls were analyzed using quantitative nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Metabolomic profiles were compared using unsupervised and supervised multivariate analyses, validated in an independent external MDS cohort, and integrated with re-analysis of publicly available RNA-sequencing datasets from purified CD14+ CMML monocytes. Results: Patients with MDS and CMML exhibited broad reductions in circulating lipoprotein-associated metabolites, including HDL-, LDL-, IDL-, and apolipoprotein-associated fractions, indicating disturbed systemic lipoprotein homeostasis. Within the discovery cohort, CMML samples showed higher concentrations of the ketone bodies 3-hydroxybutyrate and acetoacetate, as well as succinate. LC-MS analysis demonstrated selective increases in C18:1 acylcarnitine, oleic and isopalmitic acids, whereas free carnitine abundance remained unchanged. Elevated 3-hydroxybutyrate levels were not associated with mutational burden, hematologic parameters, disease risk, or immunophenotypic features. Re-analysis of public CMML monocyte transcriptomes demonstrated increased expression of genes involved in lipid uptake and intracellular lipid trafficking, including FABP5, APOE, LPL, and SLC27A2, without coordinated activation of fatty acid oxidation pathways. External cohort analysis confirmed the overall MDS-associated plasma metabolomic profile. Conclusions: MDSs and CMML are associated with reproducible alterations in systemic lipid metabolism characterized by reduced circulating lipoprotein-associated metabolites, while CMML showed more pronounced ketone body- and acylcarnitine-associated metabolic phenotype accompanied by changes in lipid-handling transcriptional programs. These findings support altered systemic lipid metabolism and carnitine-dependent fatty acid handling as characteristic features of myeloid neoplasms and provide a rationale for future functional studies investigating lipid metabolism in disease pathogenesis.<\/jats:p>","DOI":"10.3390\/metabo16090648","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:20:46Z","timestamp":1788524446000},"page":"648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systemic Metabolic Changes in Plasma of Patients with Myelodysplastic Neoplasms and Chronic Myelomonocytic Leukemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2915-2046","authenticated-orcid":false,"given":"Ekaterina","family":"Balaian","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden, Dresden University of Technology, 01307 Dresden, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, 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Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT\/UCC), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0855-8151","authenticated-orcid":false,"given":"Fabian","family":"Springer","sequence":"additional","affiliation":[{"name":"Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, 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Dresden University of Technology, 01307 Dresden, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0037-2904","authenticated-orcid":false,"given":"Michael","family":"Wulfert","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine University, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Corinna","family":"Strupp","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine University, 40225 Dusseldorf, 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