Plasma Metabolomic Profiling in Essential Thrombocythemia: Pathway-Level Alterations and Their Relationship to Treatment Status, Platelet Count, and JAK2V617F Status

@article{erdogdu2026plasma,
  title = {{Plasma Metabolomic Profiling in Essential Thrombocythemia: Pathway-Level Alterations and Their Relationship to Treatment Status, Platelet Count, and JAK2V617F Status}},
  author = {Batuhan Erdoğdu and Murat Yıldırım and Selim Sayın and Mustafa Çelebier and Ozan Kaplan and Emine Koç and Merve Nenni and Duygu Eneş Göktan and Mustafa Güney and Gül Yavuz Ermiş and Duygu Gül and Ebru Kılıç Güneş and Bilge Uğur and Melda Cömert and Meltem Aylı},
  journal = {Metabolites},
  year = {2026},
  month = oct,
  doi = {10.3390/metabo16110809},
  url = {https://www.mdpi.com/2218-1989/16/11/809},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Plasma Metabolomic Profiling in Essential Thrombocythemia: Pathway-Level Alterations and Their Relationship to Treatment Status, Platelet Count, and JAK2V617F Status
AU  - Batuhan Erdoğdu
AU  - Murat Yıldırım
AU  - Selim Sayın
AU  - Mustafa Çelebier
AU  - Ozan Kaplan
AU  - Emine Koç
AU  - Merve Nenni
AU  - Duygu Eneş Göktan
AU  - Mustafa Güney
AU  - Gül Yavuz Ermiş
AU  - Duygu Gül
AU  - Ebru Kılıç Güneş
AU  - Bilge Uğur
AU  - Melda Cömert
AU  - Meltem Aylı
PY  - 2026
DA  - 2026/10/23
JO  - Metabolites
DO  - 10.3390/metabo16110809
UR  - https://www.mdpi.com/2218-1989/16/11/809
AB  - Background/Objectives: Essential thrombocythemia (ET) is a JAK-STAT-driven myeloproliferative neoplasm with an incompletely defined metabolic phenotype. This study aimed to characterize the plasma metabolome of ET and to determine whether it differs according to JAK2V617F status, platelet count (≥450 vs. <450 × 109/L), and cytoreductive treatment. Methods: Untargeted plasma metabolomic profiling by liquid chromatography-mass spectrometry (LC-MS) was performed in 70 ET patients and 47 healthy controls. Multivariate analysis used principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) validated by nested cross-validation and permutation testing. Differentially abundant metabolites were defined by fold-change (FC > 1.5 or <0.67) and a Benjamini–Hochberg false discovery rate (q) below 0.05; identifications were annotated at Level 1 (retention time-matched authentic standards) or Level 3 (molecular formula), and pathways were examined by over-representation analysis in Reactome. Results: PCA and PLS-DA separated ET from controls (PLS-DA R2Y = 0.96; nested cross-validation Q2 = 0.91; permutation p = 0.001). Nineteen metabolites met the criteria: seven Level 1 identifications (succinate, an aminobutyrate isomer, uridine and N-acetylphenylalanine higher; proline, glucuronolactone and quinaldate lower in ET) and twelve Level 3 candidates dominated by platelet-derived eicosanoids, including 11-dehydro-thromboxane B2 (detected in 26% of controls and 99% of patients) and thromboxane B2 (4% and 84%), prostaglandin D2/E2 and B1/A1 isomers, a hydroxy-docosahexaenoic acid isomer, and corticosteroid intermediates. Reactome over-representation analysis, which rests mainly on Level 3 candidates, ranked synthesis of prostaglandins and thromboxanes and arachidonate metabolism highest (FDR 7 × 10−5), followed by fatty acid metabolism, pyrimidine catabolism and, on the basis of Level 3 candidates only, mineralocorticoid biosynthesis. The signature was similar in direction across cytoreductive-therapy, platelet-count and JAK2V617F strata. Conclusions: These exploratory data describe a plasma metabolite signature of aspirin-treated ET dominated by platelet-derived eicosanoids, together with changes in succinate and pyrimidine-related metabolites and candidate changes in corticosteroid intermediates; because aspirin exposure and disease status were fully confounded, the signature requires confirmation with targeted methods in independent cohorts.
SN  - 2218-1989
ER  -