Drug Information

Drug (ID: DG02022) and It's Reported Resistant Information

• Name: Anthracyclines
• Indication:
  In total 1 Indication(s)
  . .; .
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [1]

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Transforming growth factor beta 1 (TGFB1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myeloid leukemia
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-07; Fold-change: 6.20E-01; Z-score: 6.08E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: TGF-beta signaling pathway; Activation; hsa04350
• In Vitro Model: K562/ADR cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX8 expression.

Key Molecule: Transforming growth factor beta 1 (TGFB1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myeloid leukemia
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-07; Fold-change: 6.20E-01; Z-score: 6.08E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: TGF-beta signaling pathway; Activation; hsa04350
• In Vitro Model: HL60/ADR cells; Blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX7 expression.

Key Molecule: Transforming growth factor beta 1 (TGFB1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myeloid leukemia
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-07; Fold-change: 6.20E-01; Z-score: 6.08E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: TGF-beta signaling pathway; Activation; hsa04350
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX6 expression.

Key Molecule: Transforming growth factor beta 1 (TGFB1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myeloid leukemia
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-07; Fold-change: 6.20E-01; Z-score: 6.08E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: TGF-beta signaling pathway; Activation; hsa04350
• In Vitro Model: HL-60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX5 expression.

Key Molecule: Transforming growth factor beta 1 (TGFB1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myeloid leukemia
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-07; Fold-change: 6.20E-01; Z-score: 6.08E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: TGF-beta signaling pathway; Activation; hsa04350
• In Vitro Model: KG-1 A cells; Blood; Homo sapiens (Human); CVCL_0374
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX4 expression.

Key Molecule: Transforming growth factor beta 1 (TGFB1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Acute myeloid leukemia [ICD-11: 2A60]
• The Specified Disease: Acute myeloid leukemia
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-07; Fold-change: 6.20E-01; Z-score: 6.08E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: TGF-beta signaling pathway; Activation; hsa04350
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis

Chronic myeloid leukemia [ICD-11: 2A20]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [2]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p-glycoprotein; Regulation; N.A.
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562 ABCG2 overexpression cells; Bone marrow; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Flow Cytometry assay; DNA dye competition assay
• Mechanism Description: Exert their activity exclusively through histone eviction and are generally more cytotoxic to tumor cells than their parent compound;DNA double-strand break generation versus histone eviction;Anthracyclines featuring an N,N-dimethyl aminosugar in general are poor substrates for the ABCB1 drug transporter as compared to their non-alkylated counterparts.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p-glycoprotein; Regulation; N.A.
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562 ABCB1 overexpression cells; Bone marrow; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Flow Cytometry assay; DNA dye competition assay
• Mechanism Description: Exert their activity exclusively through histone eviction and are generally more cytotoxic to tumor cells than their parent compound;DNA double-strand break generation versus histone eviction;Anthracyclines featuring an N,N-dimethyl aminosugar in general are poor substrates for the ABCB1 drug transporter as compared to their non-alkylated counterparts.

References

• Ref 1: The roles and mechanisms of TGFB1 in acute myeloid leukemia chemoresistance. Cell Signal. 2024 Apr;116:111027.
• Ref 2: Novel N,N-Dimethyl-idarubicin Analogues Are Effective Cytotoxic Agents for ABCB1-Overexpressing, Doxorubicin-Resistant Cells. J Med Chem. 2024 Aug 22;67(16):13802-13812.