Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients
Several studies have linked bad prognoses of acute myeloid leukemia (AML) to the ability of leukemic cells to reprogram their metabolism and, in particular, their lipid metabolism. In this context, we performed “in-depth” characterization of fatty acids (FAs) and lipid species in leukemic cell lines...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/6/5988 |
| _version_ | 1797611180622086144 |
|---|---|
| author | Caroline Lo Presti Yoshiki Yamaryo-Botté Julie Mondet Sylvie Berthier Denisa Nutiu Cyrille Botté Pascal Mossuz |
| author_facet | Caroline Lo Presti Yoshiki Yamaryo-Botté Julie Mondet Sylvie Berthier Denisa Nutiu Cyrille Botté Pascal Mossuz |
| author_sort | Caroline Lo Presti |
| collection | DOAJ |
| description | Several studies have linked bad prognoses of acute myeloid leukemia (AML) to the ability of leukemic cells to reprogram their metabolism and, in particular, their lipid metabolism. In this context, we performed “in-depth” characterization of fatty acids (FAs) and lipid species in leukemic cell lines and in plasma from AML patients. We firstly showed that leukemic cell lines harbored significant differences in their lipid profiles at steady state, and that under nutrient stress, they developed common mechanisms of protection that led to variation in the same lipid species; this highlights that the remodeling of lipid species is a major and shared mechanism of adaptation to stress in leukemic cells. We also showed that sensitivity to etomoxir, which blocks fatty acid oxidation (FAO), was dependent on the initial lipid profile of cell lines, suggesting that only a particular “lipidic phenotype” is sensitive to the drug targeting of FAO. We then showed that the lipid profiles of plasma samples from AML patients were significantly correlated with the prognosis of patients. In particular, we highlighted the impact of phosphocholine and phosphatidyl-choline metabolism on patients’ survival. In conclusion, our data show that balance between lipid species is a phenotypic marker of the diversity of leukemic cells that significantly influences their proliferation and resistance to stress, and thereby, the prognosis of AML patients. |
| first_indexed | 2024-03-11T06:24:12Z |
| format | Article |
| id | doaj.art-91e7a801fdb746adb76f204aeb923eb8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:24:12Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-91e7a801fdb746adb76f204aeb923eb82023-11-17T11:42:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246598810.3390/ijms24065988Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML PatientsCaroline Lo Presti0Yoshiki Yamaryo-Botté1Julie Mondet2Sylvie Berthier3Denisa Nutiu4Cyrille Botté5Pascal Mossuz6Team “Epigenetic and Cellular Signaling”, Institute for Advanced Biosciences, University Grenoble Alpes (UGA), INSERM U1209/CNRS 5309, 38700 Grenoble, FranceTeam “Apicolipid”, Institute for Advanced Biosciences, University Grenoble Alpes (UGA), INSERM U1209/CNRS 5309, 38700 Grenoble, FranceTeam “Epigenetic and Cellular Signaling”, Institute for Advanced Biosciences, University Grenoble Alpes (UGA), INSERM U1209/CNRS 5309, 38700 Grenoble, FrancePlatform of Cytometry, Institute of Biology and Pathology, Hospital of Grenoble Alpes (CHUGA), CS 20217, 38043 Grenoble, CEDEX 9, FranceTeam “Epigenetic and Cellular Signaling”, Institute for Advanced Biosciences, University Grenoble Alpes (UGA), INSERM U1209/CNRS 5309, 38700 Grenoble, FranceTeam “Apicolipid”, Institute for Advanced Biosciences, University Grenoble Alpes (UGA), INSERM U1209/CNRS 5309, 38700 Grenoble, FranceTeam “Epigenetic and Cellular Signaling”, Institute for Advanced Biosciences, University Grenoble Alpes (UGA), INSERM U1209/CNRS 5309, 38700 Grenoble, FranceSeveral studies have linked bad prognoses of acute myeloid leukemia (AML) to the ability of leukemic cells to reprogram their metabolism and, in particular, their lipid metabolism. In this context, we performed “in-depth” characterization of fatty acids (FAs) and lipid species in leukemic cell lines and in plasma from AML patients. We firstly showed that leukemic cell lines harbored significant differences in their lipid profiles at steady state, and that under nutrient stress, they developed common mechanisms of protection that led to variation in the same lipid species; this highlights that the remodeling of lipid species is a major and shared mechanism of adaptation to stress in leukemic cells. We also showed that sensitivity to etomoxir, which blocks fatty acid oxidation (FAO), was dependent on the initial lipid profile of cell lines, suggesting that only a particular “lipidic phenotype” is sensitive to the drug targeting of FAO. We then showed that the lipid profiles of plasma samples from AML patients were significantly correlated with the prognosis of patients. In particular, we highlighted the impact of phosphocholine and phosphatidyl-choline metabolism on patients’ survival. In conclusion, our data show that balance between lipid species is a phenotypic marker of the diversity of leukemic cells that significantly influences their proliferation and resistance to stress, and thereby, the prognosis of AML patients.https://www.mdpi.com/1422-0067/24/6/5988acute myeloid leukemiametabolismlipid speciesinhibition of FAO |
| spellingShingle | Caroline Lo Presti Yoshiki Yamaryo-Botté Julie Mondet Sylvie Berthier Denisa Nutiu Cyrille Botté Pascal Mossuz Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients International Journal of Molecular Sciences acute myeloid leukemia metabolism lipid species inhibition of FAO |
| title | Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients |
| title_full | Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients |
| title_fullStr | Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients |
| title_full_unstemmed | Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients |
| title_short | Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients |
| title_sort | variation in lipid species profiles among leukemic cells significantly impacts their sensitivity to the drug targeting of lipid metabolism and the prognosis of aml patients |
| topic | acute myeloid leukemia metabolism lipid species inhibition of FAO |
| url | https://www.mdpi.com/1422-0067/24/6/5988 |
| work_keys_str_mv | AT carolinelopresti variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients AT yoshikiyamaryobotte variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients AT juliemondet variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients AT sylvieberthier variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients AT denisanutiu variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients AT cyrillebotte variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients AT pascalmossuz variationinlipidspeciesprofilesamongleukemiccellssignificantlyimpactstheirsensitivitytothedrugtargetingoflipidmetabolismandtheprognosisofamlpatients |