Disease Information

General Information of the Disease (ID: DIS00195)

• Name: Mycosis fungoides
• ICD: ICD-11: 2B01

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

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

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: C-X-C motif chemokine ligand 12 (CXCL12) [1]

• Resistant Disease: Mycosis fungoides [ICD-11: 2B01.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycosis fungoides tissue; N.A.
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: MF cultures yielded significantly increased levels of FAPalpha, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4 axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility.

Key Molecule: CXC chemokine receptor type 4 (CXCR4) [1]

• Resistant Disease: Mycosis fungoides [ICD-11: 2B01.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycosis fungoides tissue; N.A.
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: MF cultures yielded significantly increased levels of FAPalpha, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4 axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility.

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

SL111

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-155 [2]

• Resistant Disease: Mycosis fungoides [ICD-11: 2B01.0]
• Resistant Drug: SL111
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MyLa cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: MJ cells; Peripheral blood; Homo sapiens (Human); CVCL_1414
• In Vivo Model: SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Oncogenic miR-155 appears to contribute to the cancerous phenotype of MyLa and MJ cells.

Key Molecule: hsa-mir-155 [2]

• Resistant Disease: Mycosis fungoides [ICD-11: 2B01.0]
• Resistant Drug: SL111
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MyLa cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: MJ cells; Peripheral blood; Homo sapiens (Human); CVCL_1414
• In Vivo Model: SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Oncogenic miR-155 appears to contribute to the cancerous phenotype of MyLa and MJ cells.

References

• Ref 1: Cancer-Associated Fibroblasts in Mycosis Fungoides Promote Tumor Cell Migration and Drug Resistance through CXCL12/CXCR4 .J Invest Dermatol. 2021 Mar;141(3):619-627.e2. doi: 10.1016/j.jid.2020.06.034. Epub 2020 Aug 11. 10.1016/j.jid.2020.06.034
• Ref 2: Oncogenic role of microRNA-155 in mycosis fungoides: an in vitro and xenograft mouse model study .Br J Dermatol. 2017 Sep;177(3):791-800. doi: 10.1111/bjd.15422. Epub 2017 May 7. 10.1111/bjd.15422