ArticleHaematologica2017
The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.
Article in Haematologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- The role of chemokine receptors in leukemia: implications for prognosis and therapeutic strategies.Molecular biology reports · 2026Review
- T cell acute lymphoblastic leukemia exploits a neural proinflammatory pathway to colonize the meninges.The Journal of clinical investigation · 2026Article
- CD79A and IL7R mRNA Levels in the Cerebrospinal Fluid of Adults with Acute B-Cell Lymphoblastic Leukemia: A Pilot Study.Diseases (Basel, Switzerland) · 2025Article
- A novel anti-mouse CCR7 monoclonal antibody, CBiochemistry and biophysics reports · 2025Article
- Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure.HemaSphere · 2025Article
- A brain organoid/ALL coculture model reveals the AP-1 pathway as critically associated with CNS involvement of BCP-ALL.Blood advances · 2024Article
- The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia.Annals of hematology · 2024Review
- Development of combination therapies with BTK inhibitors and dasatinib to treat CNS-infiltrating E2A-PBX1+/preBCR+ ALL.Blood advances · 2024Article
- AP-1 Transcription Factor Complex MembersHemaSphere · 2023Article
- CXCR4 antagonists disrupt leukaemia-meningeal cell adhesion and attenuate chemoresistance.British journal of haematology · 2023Article
- Integrins and the Metastasis-like Dissemination of Acute Lymphoblastic Leukemia to the Central Nervous System.Cancers · 2023Review
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023Review
- Central nervous system involvement in childhood acute lymphoblastic leukemia: challenges and solutions.Leukemia · 2022Review
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- Central Nervous System Involvement in Adults with Acute Leukemia: Diagnosis, Prevention, and Management.Current oncology reports · 2022Review
- C-C Chemokine Receptor 7 in Cancer.Cells · 2022Review
- Fast H3K9 methylation promoted by CXCL12 contributes to nuclear changes and invasiveness of T-acute lymphoblastic leukemia cells.Oncogene · 2022Article
- Multiomic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target.Blood cancer discovery · 2022Article
- Leukaemia: a model metastatic disease.Nature reviews. Cancer · 2021Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central nervous system positivity in T-cell acute lymphoblastic leukemia (odds ratio=11.00, 95% confidence interval, 2.00-60.62). We propose zeta-chain-associated protein kinase 70, CCR7 and CXCR4 as markers of central nervous system infiltration in acute lymphoblastic leukemia warranting prospective investigation.
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