ArticleProceedings of the National Academy of Sciences of the United States of America2010
CD22 EXON 12 deletion as a pathogenic mechanism of human B-precursor leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell malignancies.Nature communications · 2025Article
- Hematopoietic effects of Fufang E'jiao Jiang revealed by microbiome, metabolome and transcriptome analyses: a multi-omics strategy.Frontiers in immunology · 2025Article
- Targeted therapy for leukemia based on nanomaterials.Heliyon · 2024Review
- Chromatin accessibility uncovers KRAS-driven FOSL2 promoting pancreatic ductal adenocarcinoma progression through up-regulation of CCL28.British journal of cancer · 2023Article
- Discovery, classification, evolution and diversity of Siglecs.Molecular aspects of medicine · 2023Review
- Emerging phagocytosis checkpoints in cancer immunotherapy.Signal transduction and targeted therapy · 2023Review
- CD22 Exon 12 Deletion as an Independent Predictor of Poor Treatment Outcomes in B-ALL.Cancers · 2023Article
- ERBB1/EGFR and JAK3 Tyrosine Kinases as Potential Therapeutic Targets in High-Risk Multiple Myeloma.Onco · 2022Article
- Splicing-Mediated Antigen Escape from Immunotherapy for B-cell Malignancies.Blood cancer discovery · 2022Article
- Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies.Blood cancer discovery · 2022Article
- Tyrosine kinases in KMT2A/MLL-rearranged acute leukemias as potential therapeutic targets to overcome cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- Sialylation is involved in cell fate decision during development, reprogramming and cancer progression.Protein & cell · 2019Review
- Down-regulation of siglec-2 (CD22) predicts worse overall survival from HBV-related early-stage hepatocellular carcinoma: a preliminary analysis from Gene Expression Omnibus.Bioscience reports · 2018Article
- Possible Influences of Endogenous and Exogenous Ligands on the Evolution of Human Siglecs.Frontiers in immunology · 2018Review
- Identification and targeting of CD22ΔE12 as a molecular RNAi target to overcome drug resistance in high-risk B-lineage leukemias and lymphomas.Cancer drug resistance (Alhambra, Calif.) · 2018Article
- Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity.Clinical reviews in allergy & immunology · 2017Review
- Can we be SMaRT-er in our approach to cancer therapy?EBioMedicine · 2015Article
- Development of Polypeptide-based Nanoparticles for Non-viral Delivery of CD22 RNA Trans-splicing Molecule as a New Precision Medicine Candidate Against B-lineage ALL.EBioMedicine · 2015Article
- CD22ΔE12 as a molecular target for RNAi therapy.British journal of haematology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we report that primary leukemic cells from infants with newly diagnosed B-precursor leukemia express a truncated and functionally defective CD22 coreceptor protein that is unable to transmit apoptotic signals because it lacks most of the intracellular domain, including the key regulatory signal transduction elements and all of the cytoplasmic tyrosine residues. Expression of this structurally and functionally abnormal CD22 protein is associated with a very aggressive in vivo growth of patients' primary leukemia cells causing disseminated overt leukemia in SCID mice. The abnormal CD22 coreceptor is encoded by a profoundly aberrant mRNA arising from a splicing defect that causes the deletion of exon 12 (c.2208-c.2327) (CD22ΔE12) and results in a truncating frameshift mutation. The splicing defect is associated with multiple homozygous mutations within a 132-bp segment of the intronic sequence between exons 12 and 13. These mutations cause marked changes in the predicted secondary structures of the mutant CD22 pre-mRNA sequences that affect the target motifs for the splicing factors hnRNP-L, PTB, and PCBP that are up-regulated in infant leukemia cells. Forced expression of the mutant CD22ΔE12 protein in transgenic mice perturbs B-cell development, as evidenced by B-precursor/B-cell hyperplasia, and corrupts the regulation of gene expression, causing reduced expression levels of several genes with a tumor suppressor function. We further show that CD22ΔE12-associated unique gene expression signature is a discriminating feature of newly diagnosed infant leukemia patients. These striking findings implicate CD22ΔE12 as a previously undescribed pathogenic mechanism in human B-precursor leukemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.