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. 2025 Apr 15;2(3):100105.
doi: 10.1016/j.bneo.2025.100105. eCollection 2025 Aug.

Magnetic resonance spectroscopy-based detection of response to therapy targeting glutaminolysis in lymphoma

Kavindra Nath  1 , Pradeep K Gupta  1 , Shengchun Wang  2 , Alexander A Shestov  1 , Neil Sen  2 , Shilpa Rao  2 , Stepan Orlovskiy  1 , Cosimo Lobello  2 , David Rushmore  2 , Fernando Arias-Mendoza  1   3 , Johnvesly Basappa  2 , David S Nelson  1 , Mariusz A Wasik  2
Affiliations

Magnetic resonance spectroscopy-based detection of response to therapy targeting glutaminolysis in lymphoma

Kavindra Nath et al. Blood Neoplasia. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Effect of GSL inhibitor (CB-839) on growth, proliferation, survival, and metabolism of MCL cells. (A) Results of MTT conversion assay with the depicted 6 patient-derived MCL cell lines after 72-hour incubation in vehicle (DMSO) or various concentrations of CB-839, ranging from 0 to 1000 nM. (B) Cell cycle phases with compartmentalization (R3, sub G0/G1; R4, G0/G1; R5, S; R6, M) detected after 48-hour exposure of the MCL cell populations to CB-839 or the inhibitor’s (control) medium. (C) Apoptotic cell death identified by a DNA fragmentation (TUNEL) assay after 72-hour MCL cell exposure to CB-839 vs control medium. (D) Key metabolites in MCL-SL cells. Metabolites affected by the cell treatment with CB-839, identified by Liquid Chromatography-Mass Spectrometry (LC-MS) and metabolome-targeting bioinformatics, are highlighted by green background; the CB-839–induced changes in the MCL-SL identified signals are displayed in the associated graphs (black columns, control; and red columns, CB-839). α-KG, α-ketoglutarate; CoA, Coenzyme A; DMSO, dimethyl sulfoxide; GABA, gamma-aminobutyric acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TCA, tricarboxylic acid; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
Figure 1.
Figure 1.
Effect of GSL inhibitor (CB-839) on growth, proliferation, survival, and metabolism of MCL cells. (A) Results of MTT conversion assay with the depicted 6 patient-derived MCL cell lines after 72-hour incubation in vehicle (DMSO) or various concentrations of CB-839, ranging from 0 to 1000 nM. (B) Cell cycle phases with compartmentalization (R3, sub G0/G1; R4, G0/G1; R5, S; R6, M) detected after 48-hour exposure of the MCL cell populations to CB-839 or the inhibitor’s (control) medium. (C) Apoptotic cell death identified by a DNA fragmentation (TUNEL) assay after 72-hour MCL cell exposure to CB-839 vs control medium. (D) Key metabolites in MCL-SL cells. Metabolites affected by the cell treatment with CB-839, identified by Liquid Chromatography-Mass Spectrometry (LC-MS) and metabolome-targeting bioinformatics, are highlighted by green background; the CB-839–induced changes in the MCL-SL identified signals are displayed in the associated graphs (black columns, control; and red columns, CB-839). α-KG, α-ketoglutarate; CoA, Coenzyme A; DMSO, dimethyl sulfoxide; GABA, gamma-aminobutyric acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TCA, tricarboxylic acid; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.
Figure 2.
Figure 2.
In vivo 1H MRS–detectable biomarkers of GLS inhibition vs tumor volume in MCL xenografts. The spectral peak areas of lactate (upper rows) and alanine (middle rows), normalized to the water signal, were measured by 1H MRS with an Hadamard Selective Multiquantum Coherence (HDMD-Sel-MQC) transfer pulse sequence. (A) A representative subcutaneous MCL xenograft and 1H MRS spectrum acquired with HDMD-Sel-MQC transfer pulse sequence on a 9.4T horizontal bore Bruker console. (B) MCL-SL tumor (n = 5 mice per control and CB-839–treated cohort). (C) JeKo-1 tumor (n = 5). (D) REC-1 tumor (n = 5). CB-839 was administered orally at 200 mg/kg, twice daily, with vehicle-treated controls included for each MCL tumor type.
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