PMID- 30806567
OWN - NLM
STAT- MEDLINE
DCOM- 20200507
LR  - 20210301
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 15
IP  - 5
DP  - 2019 May
TI  - Azacitidine resistance caused by LAMP2 deficiency: a therapeutic window for the 
      use of autophagy inhibitors in MDS/AML patients?
PG  - 927-929
LID - 10.1080/15548627.2019.1586259 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a selective form of autophagy that allows 
      the elimination and recycling of cytosolic proteins endowed with a KFERQ-like 
      motif into the lysosome. During this process, the proteins to be degraded are 
      recognized by cellular chaperones such as HSC70 and presented to the CMA receptor 
      LAMP2A, which then translocate them into lysosomes for degradation. In this 
      punctum, we discuss the mechanisms underlying the response and resistance to 
      Azacitidine (Aza) in MDS/AML cell lines and bone marrow CD34+ blasts from MDS/AML 
      patients. 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.
FAU - Robert, Guillaume
AU  - Robert G
AD  - a Team "Myeloid Malignancies and Multiple Myeloma" , Universite Cote d'Azur, 
      Inserm U1065/C3M , Nice , France.
FAU - Auberger, Patrick
AU  - Auberger P
AD  - a Team "Myeloid Malignancies and Multiple Myeloma" , Universite Cote d'Azur, 
      Inserm U1065/C3M , Nice , France.
LA  - eng
PT  - Comment
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190301
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (LAMP2 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Molecular Chaperones)
RN  - M801H13NRU (Azacitidine)
SB  - IM
CON - Leukemia. 2019 Jun;33(6):1501-1513. PMID: 30607021
EIN - Autophagy. 2021 Nov;17(11):3893. PMID: 33645437
MH  - *Autophagy
MH  - Azacitidine
MH  - Humans
MH  - *Leukemia, Myeloid, Acute
MH  - Lysosomal-Associated Membrane Protein 2
MH  - Lysosomes
MH  - Molecular Chaperones
PMC - PMC6526876
OTO - NOTNLM
OT  - AML
OT  - CMA
OT  - MDS
OT  - azacytidine
OT  - lysosome inhibitors
EDAT- 2019/02/27 06:00
MHDA- 2020/05/08 06:00
PMCR- 2020/03/01
CRDT- 2019/02/27 06:00
PHST- 2019/02/27 06:00 [pubmed]
PHST- 2020/05/08 06:00 [medline]
PHST- 2019/02/27 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - 1586259 [pii]
AID - 10.1080/15548627.2019.1586259 [doi]
PST - ppublish
SO  - Autophagy. 2019 May;15(5):927-929. doi: 10.1080/15548627.2019.1586259. Epub 2019 
      Mar 1.