Identification of genetic targets in acute myeloid leukaemia for designing targeted therapy.
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
29
06
2020
revised:
03
09
2020
accepted:
04
09
2020
pubmed:
7
10
2020
medline:
27
4
2021
entrez:
6
10
2020
Statut:
ppublish
Résumé
Few effective therapies exist for acute myeloid leukaemia (AML), in part due to the molecular heterogeneity of this disease. We sought to identify genes crucial to deregulated AML signal transduction pathways which, if inhibited, could effectively eradicate leukaemia stem cells. Due to difficulties in screening primary cells, most previous studies have performed next-generation sequencing (NGS) library knockdown screens in cell lines. Using carefully considered methods including evaluation at multiple timepoints to ensure equitable gene knockdown, we employed a large NGS short hairpin RNA (shRNA) knockdown screen of nearly 5 000 genes in primary AML cells from six patients to identify genes that are crucial for leukaemic survival. Across various levels of stringency, genome-wide bioinformatic analysis identified a gene in the NOX family, NOX1, to have the most consistent knockdown effectiveness in primary cells (P = 5∙39 × 10
Substances chimiques
CYBB protein, human
EC 1.6.3.-
NADPH Oxidase 2
EC 1.6.3.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
137-145Subventions
Organisme : Friends of Hammersmith Hospital
Organisme : Intermountain Healthcare and Primary Children's Hospital Foundations
Organisme : Leuka
Informations de copyright
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
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