ArticleBlood2009
BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 117 citations in OpenAlex.
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Differential expression profiles of immunoregulatory genes in anaplastic thyroid carcinomas with a coexistent papillary carcinoma component.Virchows Archiv : an international journal of pathology · 2025Article
- CRISPR screening reveals ZNF217 as a vulnerability in high-risk B-cell acute lymphoblastic leukemia.Theranostics · 2025Article
- Transcription factor networks link B-lymphocyte development and malignant transformation in leukemia.Genes & development · 2023Review
- A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis.Frontiers in immunology · 2023Article
- ErbB2/Her2-dependent downregulation of a cell death-promoting protein BLNK in breast cancer cells is required for 3D breast tumor growth.Cell death & disease · 2022Article
- Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism.Journal of natural medicines · 2022Article
- Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.Molecular biology reports · 2022Article
- Activated interleukin-7 receptor signaling drives B-cell acute lymphoblastic leukemia in mice.Leukemia · 2022Article
- Article
- C/EBPβ induces B-cell acute lymphoblastic leukemia and cooperates with BLNK mutations.Cancer science · 2021Article
- Ikaros Proteins in Tumor: Current Perspectives and New Developments.Frontiers in molecular biosciences · 2021Review
- An immune-related prognostic signature for predicting breast cancer recurrence.Cancer medicine · 2020Article
- Tubulosine selectively inhibits JAK3 signalling by binding to the ATP-binding site of the kinase of JAK3.Journal of cellular and molecular medicine · 2020Article
- Multi-Omics Analysis of Acute Lymphoblastic Leukemia Identified the Methylation and Expression Differences Between BCP-ALL and T-ALL.Frontiers in cell and developmental biology · 2020Article
- Flip the coin: IL-7 and IL-7R in health and disease.Nature immunology · 2019Review
- Article
- Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level.PloS one · 2019Article
- ErbB2-driven downregulation of the transcription factor Irf6 in breast epithelial cells is required for their 3D growth.Breast cancer research : BCR · 2018Article
- Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.Journal of cellular physiology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pre-B-cell leukemia spontaneously develops in BLNK-deficient mice, and pre-B-cell acute lymphoblastic leukemia cells in children often lack BLNK protein expression, demonstrating that BLNK functions as a tumor suppressor. However, the mechanism by which BLNK suppresses pre-B-cell leukemia, as well as the identification of other genetic alterations that collaborate with BLNK deficiency to cause leukemogenesis, are still unknown. Here, we demonstrate that the JAK3/STAT5 signaling pathway is constitutively activated in pre-B leukemia cells derived from BLNK(-/-) mice, mostly due to autocrine production of IL-7. Inhibition of IL-7R signaling or JAK3/STAT5 activity resulted in the induction of p27(kip1) expression and cell-cycle arrest, accompanied by apoptosis in the leukemia cells. Transgene-derived constitutively active STAT5 (STAT5b-CA) strongly synergized with the loss of BLNK to initiate leukemia in vivo. In the leukemia cells, exogenously expressed BLNK inhibited autocrine JAK3/STAT5 signaling, resulting in p27(kip1) induction, cell-cycle arrest, and apoptosis. BLNK-inhibition of JAK3 was dependent on the binding of BLNK to JAK3. These data indicate that BLNK normally regulates IL-7-dependent proliferation and survival of pre-B cells through direct inhibition of JAK3. Thus, somatic loss of BLNK and concomitant mutations leading to constitutive activation of Jak/STAT5 pathway result in the generation of pre-B-cell leukemia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.