ArticleProceedings of the National Academy of Sciences of the United States of America2005
Deficiency of Bruton's tyrosine kinase in B cell precursor leukemia cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 57 citations in OpenAlex.
- An antibody-drug conjugate targeting VpreB1 for the treatment of B-cell acute lymphoblastic leukemia.Blood neoplasia · 2025Article
- Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses.Nature communications · 2021Article
- Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer.Molecular cell · 2021Article
- Bruton's Tyrosine Kinase and Its Isoforms in Cancer.Frontiers in cell and developmental biology · 2021Review
- The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers.Biomolecules · 2020Review
- It Takes Three Receptors to Raise a B Cell.Trends in immunology · 2020Review
- Autoimmunity checkpoints as therapeutic targets in B cell malignancies.Nature reviews. Cancer · 2018Review
- Ibrutinib inhibits pre-BCRBlood · 2017Article
- A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation.Oncogene · 2016Article
- Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia.Scientific reports · 2015Article
- Rationale for targeting the pre-B-cell receptor signaling pathway in acute lymphoblastic leukemia.Blood · 2015Review
- Are patients with X-linked agammaglobulinemia at increased risk of developing acute lymphoblastic leukemia?Journal of clinical immunology · 2015Article
- X-linked agammaglobulinemia associated with B-precursor acute lymphoblastic leukemia.Journal of clinical immunology · 2015Review
- Bruton's tyrosine kinase: from X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Article
- Targeting Bruton's tyrosine kinase in B cell malignancies.Nature reviews. Cancer · 2014Review
- Interference with pre-B-cell receptor signaling offers a therapeutic option for TCF3-rearranged childhood acute lymphoblastic leukemia.Blood cancer journal · 2014Article
- Protein kinases: emerging therapeutic targets in chronic lymphocytic leukemia.Expert opinion on investigational drugs · 2012Review
- Compensatory signals associated with the activation of human GC 5' splice sites.Nucleic acids research · 2011Article
- Increased drug efflux along with midkine gene high expression in childhood B-lineage acute lymphoblastic leukemia cells.International journal of hematology · 2010Article
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruton's tyrosine kinase (BTK) deficiency results in a differentiation block at the pre-B cell stage. Likewise, acute lymphoblastic leukemia cells are typically arrested at early stages of B cell development. We therefore investigated BTK function in B cell precursor leukemia cells carrying a BCR-ABL1, E2A-PBX1, MLL-AF4, TEL-AML1, or TEL-PDGFRB gene rearrangement. Although somatic mutations of the BTK gene are rare in B cell precursor leukemia cells, we identified kinase-deficient splice variants of BTK throughout all leukemia subtypes. Unlike infant leukemia cells carrying an MLL-AF4 gene rearrangement, where expression of full-length BTK was detectable in only four of eight primary cases, in leukemia cells harboring other fusion genes full-length BTK was typically coexpressed with kinase-deficient variants. As shown by overexpression experiments, kinase-deficient splice variants can act as a dominant-negative BTK in that they suppress BTK-dependent differentiation and pre-B cell receptor responsiveness of the leukemia cells. On the other hand, induced expression of full-length BTK rendered the leukemia cells particularly sensitive to apoptosis. Comparing BTK expression in surviving or preapoptotic leukemia cells after 10-Gy gamma radiation, we observed selective survival of leukemia cells that exhibit expression of dominant-negative BTK forms. These findings indicate that lack of BTK expression or expression of dominant-negative splice variants in B cell precursor leukemia cells can (i) inhibit differentiation beyond the pre-B cell stage and (ii) protect from radiation-induced apoptosis.
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