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CD 22 ΔE12 as a molecular target for RNA i therapy
Author(s) -
Uckun Fatih M.,
Ma Hong,
Cheng Jianjun,
Myers Dorothea E.,
Qazi Sanjive
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13306
Subject(s) - rna interference , gene knockdown , cd22 , cancer research , targeted therapy , biology , rna , cell culture , cancer , immunology , gene , b cell , genetics , antibody
Summary B‐precursor acute lymphoblastic leukaemia ( BPL ) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD 22 ΔE12 is a characteristic genetic defect of therapy‐refractory clones in paediatric BPL and implicated the CD 22 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 CD 22 ΔE12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference ( RNA i) therapy. Here we report a previously unrecognized causal link between CD 22 ΔE12 and aggressive biology of human BPL cells by demonstrating that si RNA ‐mediated knockdown of CD 22 ΔE12 in primary leukaemic B‐cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD 22 ΔE12‐specific si RNA with potent in vitro and in vivo anti‐leukaemic activity against primary human BPL cells as a first‐in‐class RNA i therapeutic candidate targeting CD 22 ΔE12.