Disease Information

General Information of the Disease (ID: DIS00191)

• Name: Myelodysplastic syndrome
• ICD: ICD-11: 2A37

Type(s) of Resistant Mechanism of This Disease

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Azacitidine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Lysosome-associated membrane glycoprotein 2 (LAMP2) [1]

• Resistant Disease: Myelodysplastic syndrome [ICD-11: 2A37.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Azacitidine
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: We show that treatment of MDS/AML cell lines and bone marrow samples from MDS/AML patients with Aza triggers loss of LAMP2 expression leading to CMA defects. LAMP2 deficiency is responsible for CMA defects, Aza resistance and hypersensitivity to lysosome and autophagy inhibitors. Low levels of LAMP2 expression in CD34+ blasts from MDS/AML patients correlate with an absence of response to Aza and are associated to a pejorative overall survival. We propose that CD34+/LAMP2Low patients at diagnosis or who become CD34+/LAMP2Low during the course of treatment with Aza could receive an autophagy inhibitor available in the clinic.

References

• Ref 1: Azacitidine resistance caused by LAMP2 deficiency: a therapeutic window for the use of autophagy inhibitors in MDS/AML patients .Autophagy. 2019 May;15(5):927-929. doi: 10.1080/15548627.2019.1586259. Epub 2019 Mar 1. 10.1080/15548627.2019.1586259