CD22ΔE12 as a molecular target for RNAi therapy. (6th February 2015)

• Record Type: Journal Article
• Authors: Uckun, Fatih M.; Ma, Hong; Cheng, Jianjun; Myers, Dorothea E.; Qazi, Sanjive
• Is Part Of: British journal of haematology. Volume 169:Number 3(2015:May)
• Page Start: 401
• Page End: 414
• Publication Date: 2015-02-06
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13306
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13306-abs-0001"> <title>Summary</title> <p>B‐precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that <italic>CD22</italic>ΔE12 is a characteristic genetic defect of therapy‐refractory clones in paediatric BPL and implicated the <italic>CD22</italic>ΔE12 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 <italic>CD22</italic>ΔE12 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 <italic>CD22</italic>ΔE12 and aggressive biology of human BPL cells by demonstrating that siRNA‐mediated knockdown of <italic>CD22</italic>ΔE12 in primary leukaemic B‐cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of <italic>CD22</italic>ΔE12‐specific siRNA with potent <italic>in vitro</italic> and <italic>in vivo</italic> anti‐leukaemic activity against primary human BPL cells as a first‐in‐class RNAi therapeutic candidate targeting <italic>CD22</italic>ΔE12.</p> </abstract>