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CD22?E12 as a molecular target for RNAi therapy.


ABSTRACT: B-precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22?E12 is a characteristic genetic defect of therapy-refractory clones in paediatric BPL and implicated the CD22?E12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22?E12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized causal link between CD22?E12 and aggressive biology of human BPL cells by demonstrating that siRNA-mediated knockdown of CD22?E12 in primary leukaemic B-cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD22?E12-specific siRNA with potent in vitro and in vivo anti-leukaemic activity against primary human BPL cells as a first-in-class RNAi therapeutic candidate targeting CD22?E12.

SUBMITTER: Uckun FM 

PROVIDER: S-EPMC4486322 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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CD22ΔE12 as a molecular target for RNAi therapy.

Uckun Fatih M FM   Ma Hong H   Cheng Jianjun J   Myers Dorothea E DE   Qazi Sanjive S  

British journal of haematology 20150206 3


B-precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22ΔE12 is a characteristic genetic defect of therapy-refractory clones in paediatric BPL and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22ΔE12 molecular lesion in BPL and determine if it c  ...[more]

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