ArticleOncotarget2018
Up-regulation of hexokinase II contributes to rituximab-chemotherapy resistance and is a clinically relevant target for therapeutic development.
Article in Oncotarget, 2018. 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, 47 citations in OpenAlex.
- Metabolic vulnerabilities and therapeutic opportunities in diffuse large B-cell lymphoma.Oncogenesis · 2026Review
- DLBCL Cells Emerge after CD19 CAR T Cells with Cross-Antigen Resistance and a Gene Signature Predictive of Clinical CAR T-cell Response.Blood cancer discovery · 2025Article
- Mitochondrion: Main organelle in orchestrating cancer escape from chemotherapy.Cancer reports (Hoboken, N.J.) · 2024Review
- The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024Review
- Oncogenic Alterations of Metabolism Associated with Resistance to Chemotherapy.Current molecular medicine · 2024Review
- Review
- The opportunities and challenges for nutritional intervention in childhood cancers.Frontiers in nutrition · 2023Review
- Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?Cancers · 2022Review
- Targeting the immune microenvironment in mantle cell lymphoma: implications for current and emerging therapies.Leukemia & lymphoma · 2022Review
- How Do Hexokinases Inhibit Receptor-Mediated Apoptosis?Biology · 2022Review
- Molecular Aspects of Resistance to Immunotherapies-Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma.International journal of molecular sciences · 2022Review
- Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas.Frontiers in oncology · 2022Review
- Detachment of Hexokinase II From Mitochondria Promotes Collateral Sensitivity in Multidrug Resistant Chronic Myeloid Leukemia Cells.Frontiers in oncology · 2022Article
- Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.Biomedicines · 2021Review
- Small Hexokinase 1 Peptide against Toxic SOD1 G93A Mitochondrial Accumulation in ALS Rescues the ATP-Related Respiration.Biomedicines · 2021Article
- Oncogenic Mechanisms and Therapeutic Targeting of Metabolism in Leukemia and Lymphoma.Cold Spring Harbor perspectives in medicine · 2021Review
- Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters.International journal of molecular sciences · 2021Review
- Elevated Serum Lactate in Patients With Lymphoma: It Is Not Always Infection.Mayo Clinic proceedings. Innovations, quality & outcomes · 2021Article
- SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis.Nature communications · 2021Article
- Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to identify cellular pathways associated with therapy-resistant aggressive lymphoma, we generated rituximab-resistant cell lines (RRCL) and found that the acquirement of rituximab resistance was associated with a deregulation in glucose metabolism and an increase in the apoptotic threshold leading to chemotherapy resistance. Hexokinase II (HKII), the predominant isoform overexpressed in cancer cells, has dual functions of promoting glycolysis as well as inhibiting mitochondrial-mediated apoptosis. We found that RRCL demonstrated higher HKII levels. Targeting HKII resulted in decreased mitochondrial membrane potential, ATP production, cell viability; and re-sensitization to chemotherapy agents. Analyzed gene expression profiling data from diffuse large B-cell lymphoma patients, high-HKII levels were associated with a shorter progression free survival (PFS) and/or overall survival (OS). Our data suggest that over-expression of HKII is associated with resistance to rituximab and chemotherapy agents in aggressive lymphoma and identifies this enzyme isoform as a potential therapeutic target.
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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.