Abstract
Background：The lipid metabolomic profile has been well defined in the pathogenesis and differential diagnosis in patients with different myeloid diseases. However, the role of plasma lipidome was rarely explored, especially in aplastic anemia (AA), a disease which has close connection with lipid metabolism.Methods: Peripheral fasting serum levels of patients newly diagnosed with AA from March 2019 to December 2019 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the serum lipid profiles. Meanwhile, the lipidomes for patients with hypocellular myelodysplastic syndrome (h-MDS) and age and sex matched healthy volunteers were taken as controls. The lipid profiles were tested again 6 months after standard cyclosporin A（CsA）treatment in patients with AA. For all the patients, those with a history of hyperlipidemia, diabetes, obesity (body mass index > 28 kg/m 2) or complications with other malignant diseases at diagnosis were excluded.Results: The study enrolled 15 patients with AA, 11 patients with h-MDS and 20 healthy controls. All the enrolled AA patients were non-severe and transfusion dependent, and were treated with CsA 3-5mg/kg/d for at least 6 months. For h-MDS patients, five were MDS with single lineage dysplasia, three were MDS with multilineage dysplasia, and three were MDS-Excess Blasts 1 (MDS-RAEB1). Metabolites in arachidonic acid pathway and retinol metabolism were significantly decreased in the AA patients compared with the healthy controls (P<0.05). AA patients had decreased arachidonic acid pathway metabolites and retinol metabolism-related metabolites as compared with h-MDS（P<0.05), whereas h-MDS patients had increased metabolism of proline and threonine and abnormal sphingolipid metabolism compared with AA patients and the normal controls. After 6-month of CsA treatment, leukotriene B4, 15(S)-HETE, all-trans-retinal and protectin D1 decreased significantly. Patients who had response to CsA had higher levels of baseline protectin D1 (p=0.011), leukotriene B4 (p=0.011), 15(S)-HETE (p=0.004) and all-trans-retinal (p=0.000) than those who had no response.Conclusion: The lipid profiles showed significant difference not only between patients with AA and healthy controls, but also between AA and h-MDS. Meanwhile, some of baseline value and the change in lipid molecules may predict the CsA response at 6 months. DisclosuresNo relevant conflicts of interest to declare.
Highlights
Aplastic anemia (AA) is a bone marrow failure disease characterized by reduced bone marrow hematopoietic cell proliferation and peripheral blood cytopenia
Studies found that the serum sphingomyelin species containing saturated odd chain fatty acids (OCFAs) in the side chain were lower in leukemia and MDS patients compared to normal serum
There is a long history of research on lipid profiles and lipid metabolism in hematological diseases
Summary
Aplastic anemia (AA) is a bone marrow failure disease characterized by reduced bone marrow hematopoietic cell proliferation and peripheral blood cytopenia. Immunosuppressive treatment has led to remissions in 50–70% of AA patients [1], approximately 15–20% of them develop secondary MDS/acute myeloid leukemia by the 10-year followup [2]. Metabolomics, especially lipidomics, has increasing great attention as a promising tool for biomarker discovery. It had been used in the early diagnosis, progression and treatment for cancer and other diseases. With regard to hematological diseases, the lipid metabolomic profile was found to be different in the different myeloid diseases [3]. Studies found that the serum sphingomyelin species containing saturated odd chain fatty acids (OCFAs) in the side chain were lower in leukemia and MDS patients compared to normal serum. Few studies focused on the lipid profiles of AA yet
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