Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies.
Sisi ZhengElisabeth GillespieAmmar S NaqviKatharina E HayerZhiwei AngManuel Torres-DizMathieu Quesnel-VallièresDavid A HottmanAsen BagashevJohn ChukinasCarolin SchmidtMukta AsnaniRawan ShraimDeanne M TaylorSusan R RheingoldMaureen M O'BrienNathan SinghKristen W LynchMarco RuellaYoseph BarashSarah K TasianAndrei Thomas-TikhonenkoPublished in: Blood cancer discovery (2022)
The mechanism(s) underlying downregulation of surface CD22 following CD22-directed immunotherapy remains underexplored. Our biochemical and correlative studies demonstrate that in B-ALL, CD22 expression levels are controlled by inclusion/skipping of CD22 exon 2. Thus, aberrant splicing of CD22 is an important driver/biomarker of de novo and acquired resistance to CD22-directed immunotherapies. See related commentary by Bourcier and Abdel-Wahab, p. 87. This article is highlighted in the In This Issue feature, p. 85.