Drug Information

Drug (ID: DG00200) and It's Reported Resistant Information

• Name: Dexamethasone
• Synonyms: Adexone; Anaflogistico; Aphtasolon; Aphthasolone; Auxiron; Azium; Calonat; Corson; Corsone; Cortisumman; DXM; Decacort; Decacortin; Decaderm; Decadron; Decagel; Decaject; Decalix; Decameth; Decasone; Decaspray; Dectancyl; Dekacort; Deltafluorene; Dergramin; Deronil; Desadrene; Desametasone; Desamethasone; Desameton; Deseronil; Dexacort; Dexacortal; Dexacortin; Dexadeltone; Dexafarma; Dexair; Dexalona; Dexaltin; Dexametasona; Dexameth; Dexamethansone; Dexamethasonum; Dexamethazone; Dexamonozon; Dexapolcort; Dexaprol; Dexason; Dexasone; Dexinolon; Dexinoral; Dexone; Dexonium; Dexpak; Dextelan; Dezone; Dinormon; Dxms; Fluormethylprednisolone; Fluormone; Fluorocort; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; IontoDex; Loverine; Luxazone; Maxidex; Mediamethasone; Methylfluorprednisolone; Mexidex; Millicorten; Mymethasone; Oradexon; Policort; Posurdex; Prodex; Spoloven; Superprednol; Turbinaire; Visumetazone; Alcon Brand of Dexamethasone; Bisu DS; Desametasone [DCIT]; Dexa Mamallet; Dexamethasone Base; Dexamethasone Intensol; Dexamethasone alcohol; ECR Brand of Dexamethasone; Foy Brand of Dexamethasone; Hexadrol Elixir; Hexadrol Tablets; ICN Brand of Dexamethasone; Lokalison F; Merck Brand of Dexamethasone; Pet Derm III; Prednisolon F; Prednisolone F; Sunia Sol D; Dexone 4; MK 125; Merz Brand 1 of Dexamethasone; Merz Brand 2 of Dexamethasone; Aeroseb-D; Aeroseb-Dex; Azium (Veterinary); Decadron (TN); Decadron Tablets, Elixir; Decadron, Dexamethasone; Decadron-LA; Dex-ide; Dexa-Cortidelt;Dexa-Cortisyl; Dexa-Mamallet; Dexa-Scheroson; Dexa-sine; Dexacen-4; Dexametasona [INN-Spanish]; Dexamethasonum [INN-Latin]; Dexone 0.5; Dexone 0.75; Dexone 1.5; Hl-dex; Isopto-Dex; OTO-104; Ocu-trol;Pet-Derm Iii; SK-Dexamethasone; Decaject L.A.; Dexamethasone [INN:BAN:JAN]; Decaject-L.A.; Dexamethasone (JP15/USP/INN); Delta1-9alpha-Fluoro-16alpha-methylcortisol; Delta(sup 1)-9-alpha-Fluoro-16-alpha-methylcortisol; (3H)-Dexamethasone; 1-Dehydro-16.alpha.-methyl-9.alpha.-fluorohydrocortisone; 1-Dehydro-16alpha-methyl-9alpha-fluorohydrocortisone; 16-alpha-Methyl-9-alpha-fluoro-1-dehydrocortisol; 16-alpha-Methyl-9-alpha-fluoro-delta(sup 1)-hydrocortisone; 16-alpha-Methyl-9-alpha-fluoro-delta1-hydrocortisone; 16-alpha-Methyl-9-alpha-fluoroprednisolone; 16.alpha.-Methyl-9.alpha.-fluoro-1-dehydrocortisol; 16.alpha.-Methyl-9.alpha.-fluoroprednisolone; 16alpha-Methyl-9alpha-fluoro-1-dehydrocortisol; 16alpha-Methyl-9alpha-fluoro-delta(sup 1)-hydrocortisone; 16alpha-Methyl-9alpha-fluoroprednisolone; 9-alpha-Fluoro-16-alpha-methylprednisolone; 9.alpha.-Fluoro-16.alpha.-methylprednisolone; 9A-FLUORO-16BETA-METHYLPREDNISOLONE; 9alpha-Fluoro-16alpha-methylprednisolone
• Indication:
  In total 1 Indication(s)
  Rheumatoid arthritis [ICD-11: FA20]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (4 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [2]
  Acute myeloid leukemia [ICD-11: 2A60]; [3], [4]
  Multiple myeloma [ICD-11: 2A83]; [5]
  Rheumatoid arthritis [ICD-11: FA20]; [6]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [1]
  Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]; [7]
• Target: Glucocorticoid receptor (NR3C1); GCR_HUMAN; [1]
• Formula: C22H29FO5
• IsoSMILES: C[C@@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)CO)O)C)O)F)C
• InChI: 1S/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15+,16+,17+,19+,20+,21+,22+/m1/s1
• InChIKey: UREBDLICKHMUKA-CXSFZGCWSA-N
• PubChem CID: 5743
• ChEBI ID: CHEBI:41879
• TTD Drug ID: D0IT2G
• VARIDT ID: DR00215
• DrugBank ID: DB01234

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Inflammation [ICD-11: 1A00-CA43]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [8]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Inflammation [ICD-11: 1A00-CA43]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Adult male CF-1 abcb1a(+/+) mice moodel; Crl:CF1- abcb1a(-/-) mice model; Mus musculus
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), contributes to highly lipophilic molecules penetrating the brain from the blood at a much lower rate than expected, and has numerous substrates, inhibitors and modulators. Dexamethasone was shown to be transported in vitro by abcb1b and showed little to no transport by abcb1a; however, in vivo tissue accumulation of dexamethasone was increased in abcb1a-deficient mice compared to abcb1a-deficien.

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

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: CREB-binding protein (CREBBP) [3], [4]

• Molecule Alteration: Mutation; .
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Next-generation sequencing assay; Exome sequencing assay; Transcriptome sequencing assay; Whole genome sequencing assay; Sanger Sequencing assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Several of these alterations are known to induce a more stem cell-like state (eg, IkZF1) or confer resistance directly to specific chemotherapy agents such as CREBBP and glucocorticoids and mutations in the 5-nucleotidase gene NT5C2 and nucleoside a.logs. Many relapse-acquired lesions are enriched in specific pathways, including B-cell development (IkZF1), tumor suppression (TP53),34 Ras signaling, chromatin modification (CREBBP, SETD2),17 and drug metabolism (NT5C2).

Multiple myeloma [ICD-11: 2A83]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [9]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: ANBL6 cells; Peripheral blood; Homo sapiens (Human); CVCL_5425
• In Vitro Model: JJN-3 cells; Bone marrow; Homo sapiens (Human); CVCL_2078
• In Vitro Model: MM1R cells; Peripheral blood; Homo sapiens (Human); CVCL_8794
• In Vitro Model: MM1S cells; Peripheral blood; Homo sapiens (Human); CVCL_8792
• In Vitro Model: OPM-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: RPMI-8226 cells; Peripheral blood; Homo sapiens (Human); CVCL_0014
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR193a/MCL1 pathway. NEAT1 promotes MM cell DEX resistance by competitively binding miR193a.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-mir-15 [5]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC) with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells.

Key Molecule: hsa-mir-16 [5]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC) with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) [9]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: ANBL6 cells; Peripheral blood; Homo sapiens (Human); CVCL_5425
• In Vitro Model: JJN-3 cells; Bone marrow; Homo sapiens (Human); CVCL_2078
• In Vitro Model: MM1R cells; Peripheral blood; Homo sapiens (Human); CVCL_8794
• In Vitro Model: MM1S cells; Peripheral blood; Homo sapiens (Human); CVCL_8792
• In Vitro Model: OPM-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: RPMI-8226 cells; Peripheral blood; Homo sapiens (Human); CVCL_0014
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR193a/MCL1 pathway. NEAT1 promotes MM cell DEX resistance by competitively binding miR193a.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-193a [9]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR193a/MCL1 signaling pathway; Activation; hsa05206
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: ANBL6 cells; Peripheral blood; Homo sapiens (Human); CVCL_5425
• In Vitro Model: JJN-3 cells; Bone marrow; Homo sapiens (Human); CVCL_2078
• In Vitro Model: MM1R cells; Peripheral blood; Homo sapiens (Human); CVCL_8794
• In Vitro Model: MM1S cells; Peripheral blood; Homo sapiens (Human); CVCL_8792
• In Vitro Model: OPM-2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: RPMI-8226 cells; Peripheral blood; Homo sapiens (Human); CVCL_0014
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR193a/MCL1 pathway.

Key Molecule: hsa-mir-137 [10]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Regulation; hsa04151
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: RPMI-8226 cells; Peripheral blood; Homo sapiens (Human); CVCL_0014
• In Vivo Model: BALB/c nu/nu nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Real Time RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-MET expression and further decreasing the AkT phosphorylation via targeting MITF.

Key Molecule: hsa-mir-202 [11]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: JNk/SAPk signaling pathway; Regulation; hsa05161
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: WST assay
• Mechanism Description: miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNk/SAPk signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Microphthalmia-associated transcription factor (MITF) [10]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Regulation; hsa04151
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vitro Model: RPMI-8226 cells; Peripheral blood; Homo sapiens (Human); CVCL_0014
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-MET expression and further decreasing the AkT phosphorylation via targeting MITF.

Key Molecule: Tumor necrosis factor ligand superfamily member 13B (TNFSF13B) [11]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Multiple myeloma [ICD-11: 2A83.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: JNk/SAPk signaling pathway; Regulation; hsa05161
• In Vitro Model: U266 cells; Bone marrow; Homo sapiens (Human); CVCL_0566
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: WST assay
• Mechanism Description: miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNk/SAPk signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells.

Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: ROR1 antisense RNA 1 (ROR1-AS1) [7]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Granta cells; Peripheral blood; Homo sapiens (Human); N.A.
• In Vitro Model: JVM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1319
• In Vitro Model: Mino cells; Peripheral blood; Homo sapiens (Human); CVCL_UW35
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: 3H-thymidine incorporation assay
• Mechanism Description: Overexpression of ROR1-AS1 LncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [12]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Baculoviral IAP repeat-containing protein 5 (BIRC5) [12]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [12]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Baculoviral IAP repeat-containing protein 5 (BIRC5) [12]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Burkitt lymphoma [ICD-11: 2A85.6]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HS-Sultan cells; Ascites; Homo sapiens (Human); CVCL_2516
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue dye exclusion assay
• Mechanism Description: MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: CREB-binding protein (CREBBP) [2]

• Molecule Alteration: Mutation; .
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Whole-exome sequencing assay; Whole-genome sequencing assay
• Experiment for Drug Resistance: Flow cytometric analysis assay; MTT assay
• Mechanism Description: However, our analysis of protein-protein interaction networks of relapse-associated mutant factors supports that, at least in part, relapse-associated mutations may converge in common nodes related to escape from DNA damage response(TP53) and glucocorticoid resistance(CREBBP and NR3C1).

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOXA cluster antisense RNA 2 (HOXA-AS2) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGFR/RAS/RAF/MEK/ERK signaling pathway; Activation; hsa01521
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEk/ERk pathway.

Key Molecule: hsa-mir-124 [13]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• In Vitro Model: CEM/C1 cells; Peripheral blood; Homo sapiens (Human); CVCL_3496
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR124 contributes to glucocorticoid resistance in acute lymphoblastic leukemia by promoting proliferation, inhibiting apoptosis and targeting NR3C1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Homeobox protein Hox-A3 (HOXA3) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGFR/RAS/RAF/MEK/ERK signaling pathway; Activation; hsa01521
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEk/ERk pathway.

Key Molecule: Glucocorticoid receptor (NR3C1) [13]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• In Vitro Model: CEM/C1 cells; Peripheral blood; Homo sapiens (Human); CVCL_3496
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: miR124 contributes to glucocorticoid resistance in acute lymphoblastic leukemia by promoting proliferation, inhibiting apoptosis and targeting NR3C1.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-210 [14]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Paediatric acute lymphocytic leukemia [ICD-11: 2B33.4]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MLL/AF4+ RS4 cells; Blood; Homo sapiens (Human); CVCL_0093
• In Vitro Model: TEL/AML1+ Reh cells; Blood; Homo sapiens (Human); CVCL_ZV66
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CellTiter 96 aqueous one solution cell proliferation assay
• Mechanism Description: Functioning as a hypoxamir (i.e. a microRNA whose expression is upregulated by hypoxia), miR-210 targets many genes involved in a wide range of physiological processes, such as cell survival/proliferation, mitochondrial metabolism, protein modification/transport, DNA damage repair and angiogenesis. Increasing/decreasing miR-210 expression using agomir/antagomir could enhance or reduce the response of Reh cells and RS4;11 cells to daunorubicin/dexamethasone/L-asparaginase and daunorubicin/dexamethasone/vincristine, respectively. miR-210 may be a good prognostic factor and a useful predictor of drug sensitivity, and is a potential therapeutic target for pediatric ALL.

ICD-04: Immune system diseases

Allergy [ICD-11: 4A85]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [8]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Allergy [ICD-11: 4A85.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Adult male CF-1 abcb1a(+/+) mice moodel; Crl:CF1- abcb1a(-/-) mice model; Mus musculus
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), contributes to highly lipophilic molecules penetrating the brain from the blood at a much lower rate than expected, and has numerous substrates, inhibitors and modulators. Dexamethasone was shown to be transported in vitro by abcb1b and showed little to no transport by abcb1a; however, in vivo tissue accumulation of dexamethasone was increased in abcb1a-deficient mice compared to abcb1a-deficien.

ICD-15: Musculoskeletal/connective-tissue diseases

Rheumatoid arthritis [ICD-11: FA20]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [6]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

ICD-21: Symptoms/clinical signs/unclassified clinical findings

Shock [ICD-11: MG40]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [8]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Shock [ICD-11: MG40.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Adult male CF-1 abcb1a(+/+) mice moodel; Crl:CF1- abcb1a(-/-) mice model; Mus musculus
• Mechanism Description: The multidrug resistance transporter, P-glycoprotein (P-gp), contributes to highly lipophilic molecules penetrating the brain from the blood at a much lower rate than expected, and has numerous substrates, inhibitors and modulators. Dexamethasone was shown to be transported in vitro by abcb1b and showed little to no transport by abcb1a; however, in vivo tissue accumulation of dexamethasone was increased in abcb1a-deficient mice compared to abcb1a-deficien.

References

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