Disease Information

General Information of the Disease (ID: DIS00192)

• Name: Acute lymphoblastic leukaemia
• ICD: ICD-11: 2A70

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cytarabine

Drug Sensitive Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-652-3p [1]

• Sensitive Disease: Lymphoblastic lymphoma [ICD-11: 2A70.0]
• Sensitive Drug: Cytarabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Pediatric ALL patients; Homo sapiens
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Drug Sensitivity Assay
• Mechanism Description: Overexpression of miR-652-3p using agomir increased the sensitivity to vincristine and cytarabine (all p<0.05) and promoted apoptosis (both p<0.05) in Reh and RS4:11 cells.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Bromodomain containing 2 (BRD2) [2]

• Resistant Disease: Lymphoblastic lymphoma [ICD-11: 2A70.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: RasGRP1/Ras/ERK signaling pathway; Activation; hsa04010
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: SUP-T1 cells; Pleural effusion; Homo sapiens (Human); CVCL_1714
• In Vitro Model: MEK-293 cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vivo Model: BALB/C-nu/nu athymic nude mice model; Mus musculus
• Experiment for Molecule Alteration: sqRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The expression of BRD2 was upregulated in drug-resistant adult T-LBL samples. Functional studies of BRD2 further demonstrated the critical role of BRD2. BRD2 induces drug resistance of T-LBL by activating the MEK/ERK/c-Myc signaling pathway.

Key Molecule: Bromodomain containing 2 (BRD2) [2]

• Resistant Disease: Lymphoblastic lymphoma [ICD-11: 2A70.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: RasGRP1/Ras/ERK signaling pathway; Activation; hsa04010
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: SUP-T1 cells; Pleural effusion; Homo sapiens (Human); CVCL_1714
• In Vitro Model: MEK-293 cells; Blood vessel; Homo sapiens (Human); N.A.
• In Vivo Model: BALB/C-nu/nu athymic nude mice model; Mus musculus
• Experiment for Molecule Alteration: sqRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The expression of BRD2 was upregulated in drug-resistant adult T-LBL samples. Functional studies of BRD2 further demonstrated the critical role of BRD2. BRD2 induces drug resistance of T-LBL by activating the MEK/ERK/c-Myc signaling pathway.

Vincristine

Drug Sensitive Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-652-3p [1]

• Sensitive Disease: Lymphoblastic lymphoma [ICD-11: 2A70.0]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Pediatric ALL patients; Homo sapiens
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Drug Sensitivity Assay
• Mechanism Description: Overexpression of miR-652-3p using agomir increased the sensitivity to vincristine and cytarabine (all p<0.05) and promoted apoptosis (both p<0.05) in Reh and RS4:11 cells.

References

• Ref 1: Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab ResistanceMol Cancer Ther. 2018 Feb;17(2):521-531. doi: 10.1158/1535-7163.MCT-17-0575. Epub 2017 Nov 20.
• Ref 2: BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma .Cancer Commun (Lond). 2020 Jun;40(6):245-259. doi: 10.1002/cac2.12039. Epub 2020 May 27. 10.1002/cac2.12039