ArticleLeukemia2019
Blocking ATM-dependent NF-κB pathway overcomes niche protection and improves chemotherapy response in acute lymphoblastic leukemia.
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Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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25citing papers in PubMed, 1 pooled it
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- Phase 2 study of combination chemotherapy with bortezomib in children with relapsed and refractory acute lymphoblastic leukemia.International journal of hematology · 2023Trial
- Interleukin-27 remodels the bone marrow niche to suppress B-cell development and leukaemia progression in mouse models.EBioMedicine · 2026Article
- Profiles of Growth Factors Secreted by In Vitro-Stimulated Paediatric Acute Leukaemia Blasts of Myeloid and Lymphoid Origin.International journal of molecular sciences · 2026Article
- The structure and functions of TRAF families and recent advances of TRAFs in leukemia.Frontiers in oncology · 2026Review
- Relationship between AQP5 and chemotherapy resistance in colorectal cancer cells and its mechanism.Discover oncology · 2025Article
- Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025Review
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- Actin-related protein 2/3 complex subunit 1B promotes ovarian cancer progression by regulating the AKT/PI3K/mTOR signaling pathway.Journal of translational internal medicine · 2024Article
- Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity.Journal of cancer research and clinical oncology · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Article
- [Progress in molecular mechanisms and targeted therapies of persistent cancer cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- Review
- Targeting DNA polymerase β elicits synthetic lethality with mismatch repair deficiency in acute lymphoblastic leukemia.Leukemia · 2023Article
- NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2023Review
- STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression.Breast cancer research and treatment · 2022Article
- Article
- Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients.Bone marrow transplantation · 2022Article
- PARP-1 inhibitors enhance the chemosensitivity of leukemia cells by attenuating NF-кB pathway activity and DNA damage response induced by IdarubicinActa biochimica et biophysica Sinica · 2022Article
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Authors and funding
26 authors at 4 institutions in 1 country.
Ya-Li ChenKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Chao TangKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Meng-Yi ZhangKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Wen-Li HuangDepartment of Pathology, School of Basic Medical Sciences, Central South University, 410013, Changsha, China.
Yan XuKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Hui-Yin SunKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Fan YangKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Li-Li SongKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
He WangKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Li-Li MuKey Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, 200025, Shanghai, China.
Ming-Hao LiKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Wei-Wei ZhengKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Yan MiaoKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Li-Xia DingKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Ben-Shang LiKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Shu-Hong ShenKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Sheng-Li LiuKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Hui LiKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Zhong-Qun ZhuDepartment of Cardiothoracic Surgery, Heart Center, Shanghai Children's Medical Center, SJTU-SM, 200025, Shanghai, China.
Hui-Wen ChenDepartment of Cardiothoracic Surgery, Heart Center, Shanghai Children's Medical Center, SJTU-SM, 200025, Shanghai, China.
Zhong-Hua TangKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Jing ChenKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China.
Deng-Li HongKey Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, SJTU-SM, 200025, Shanghai, China.ORCID http://orcid.org/0000-0001-5251-0297
Hong-Zhuan ChenKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China. hongzhuan_chen@hotmail.com.
Cai-Wen DuanKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China. duancaiwen@scmc.com.cn.
Bin-Bing S ZhouKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200025, Shanghai, China. zhoubinbing@scmc.com.cn.
Shanghai Jiao Tong University · CNMinistry of Education of the People's Republic of China · CNShanghai Children's Medical Center · CNCentral South University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.
Indexed as
AnimalsAntineoplastic AgentsAtaxia Telangiectasia Mutated ProteinsCell Line, TumorChildCytokinesDrug Resistance, NeoplasmFemaleGene Expression Regulation, LeukemicHumansMiceMice, Inbred NODMice, SCIDNF-kappa BPrecursor Cell Lymphoblastic Leukemia-LymphomaSignal TransductionAntineoplastic AgentsAtaxia Telangiectasia Mutated ProteinsATM protein, humanCytokinesNF-kappa BTNF Receptor-Associated Factor 6
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