Correcting Aberrant Splicing of the Human CD22 Gene

DESCRIPTION (provided by applicant): B-precursor acute lymphoblastic leukemia (BPL) is the most common form of cancer in children and adolescents. This project addresses an urgent and unmet need for the treatment of aggressive, treatment refractory BPL. Two recent studies have found a deletion of CD22 exon 12 (CD22?E12) in primary leukemic cells in the vast majority of pediatric patients with poor prognosis, newly diagnosed, or relapsed BPL. RT-PCR analysis of primary leukemic cells in matched pair diagnosis vs. induction failure specimens, and diagnosis vs. 1st bone marrow relapse specimens provided direct evidence that the CD22?E12 genetic defect is detectable at the time of initial diagnosis in therapy-refractory pediatric ALL patients. Preliminary studies support the hypothesis that correction of CD22?E12 results in the loss of self-renewal capacity and significantly reduces the clonogenicity of leukemic cells. We intend to develop the therapeutic potential of an RNA technology that corrects expression of