Chlorpromazine eliminates acute myeloid leukemia cells by perturbing subcellular localization of FLT3-ITD and KIT-D816V.
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Chlorpromazine
/ pharmacology
Female
HL-60 Cells
Humans
Leukemia, Myeloid, Acute
/ genetics
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Monomeric Clathrin Assembly Proteins
/ genetics
Point Mutation
Proto-Oncogene Proteins c-kit
/ genetics
Signal Transduction
/ drug effects
Tandem Repeat Sequences
/ genetics
Transplantation, Heterologous
Young Adult
fms-Like Tyrosine Kinase 3
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 08 2020
18 08 2020
Historique:
received:
21
08
2018
accepted:
13
07
2020
entrez:
20
8
2020
pubmed:
20
8
2020
medline:
17
9
2020
Statut:
epublish
Résumé
Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITD- or KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3- or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34
Identifiants
pubmed: 32811837
doi: 10.1038/s41467-020-17666-8
pii: 10.1038/s41467-020-17666-8
pmc: PMC7434901
doi:
Substances chimiques
Antineoplastic Agents
0
Monomeric Clathrin Assembly Proteins
0
PICALM protein, human
0
FLT3 protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-kit
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Chlorpromazine
U42B7VYA4P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4147Références
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