Disease Information

General Information of the Disease (ID: DIS00549)

• Name: Acute lymphocytic leukemia
• ICD: ICD-11: 2B33

Type(s) of Resistant Mechanism of This Disease

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Prednisolone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Glutamate dehydrogenase 1 (GLUD1) [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Resistant Drug: Prednisolone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Sup-PR cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Key Molecule: Glutamate dehydrogenase 2 (GLUD2) [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Resistant Drug: Prednisolone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SEM-K2 cells; Blood; Homo sapiens (Human); CVCL_S906
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Key Molecule: Alanine-serine-cysteine transporter 2 (ASCT2) [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Resistant Drug: Prednisolone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Key Molecule: Alanine-serine-cysteine transporter 3 (ASCT3) [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Resistant Drug: Prednisolone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SEM cells; Blood; Homo sapiens (Human); CVCL_0095
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

References

• Ref 1: Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells. Int J Mol Sci. 2023 Feb 8;24(4):3378.