CD22ΔE12 as a molecular target for RNAi therapy

Fatih M. Uckun, Hong Ma, Jianjun Cheng, Dorothea E. Myers, Sanjive Qazi

Research output: Contribution to journalArticlepeer-review


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 could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized causal link between CD22ΔE12 and aggressive biology of human BPL cells by demonstrating that siRNA-mediated knockdown of CD22ΔE12 in primary leukaemic B-cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD22ΔE12-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 CD22ΔE12.

Original languageEnglish (US)
Pages (from-to)401-414
Number of pages14
JournalBritish Journal of Haematology
Issue number3
StatePublished - May 1 2015
Externally publishedYes


  • Acute leukaemia
  • Childhood haematological malignancies
  • Experimental therapies
  • Molecular pathogenesis
  • New drugs for leukaemia

ASJC Scopus subject areas

  • Hematology


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