ArticleMolecular cancer research : MCR2013
Dynamic chemotherapy-induced upregulation of CXCR4 expression: a mechanism of therapeutic resistance in pediatric AML.
Article in Molecular cancer research : MCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 99 citations in OpenAlex.
- Mitochondrial transfer in acute myeloid leukaemia and multiple myeloma: Mechanisms, consequences and potential therapeutic opportunities.The FEBS journal · 2026Review
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- CXCR4 antagonistic lipid nanoparticles loading siRNA combat refractory AML through AML1-ETO depletion and homoharringtonine sensitization.Materials today. Bio · 2026Article
- Efficacy of targeted chemokine receptor 4 PET/CT in evaluating active lesions in multiple myeloma, comparison toCancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Mapping CSC-Mediated Ovarian Cancer Chemoresistance via CXCR4-PET to Guide Precision Cisplatin Re-Sensitization Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Construction and Validation of an N7-Methylguanosine-Related Prognostic Model for Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Article
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- Targeted Penetrating Motif Engineering of BH3 Mimetic: Harnessing Non-Canonical Amino Acids for Coinhibition of MCL-1 and BCL-xL in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CXCR4 as a therapeutic target in acute myeloid leukemia.Leukemia · 2024Review
- Remodeling of the bone marrow microenvironment during acute myeloid leukemia progression.Annals of translational medicine · 2024Review
- Leukemia circulation kinetics revealed through blood exchange method.Communications biology · 2024Article
- Theranostics in Hematooncology.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- CXCR4-targeted theranostics in oncology.European journal of nuclear medicine and molecular imaging · 2022Review
- The genesis and evolution of acute myeloid leukemia stem cells in the microenvironment: From biology to therapeutic targeting.Cell death discovery · 2022Review
- Article
- Leukemic stem cell signatures in Acute myeloid leukemia- targeting the Guardians with novel approaches.Stem cell reviews and reports · 2022Review
- One-Chip Isolation of Drug-Resistant Acute Myeloid Leukemia Cells with CXCR4-Targeted Magnetic Fluorescent Nanoprobes.Nanomaterials (Basel, Switzerland) · 2022Article
- Identification of biomarkers, pathways and potential therapeutic target for docetaxel resistant prostate cancer.Bioengineered · 2021Article
- Role of CXCR4 in the progression and therapy of acute leukaemia.Cell proliferation · 2021Review
- Leukaemia: a model metastatic disease.Nature reviews. Cancer · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledCure rates in pediatric acute leukemias remain suboptimal. Overexpression of the cell-surface chemokine receptor CXCR4 is associated with poor outcome in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Certain nonchemotherapeutic agents have been shown to modulate CXCR4 expression and alter leukemia interactions with stromal cells in the bone marrow microenvironment. Because chemotherapy is the mainstay of AML treatment, it was hypothesized that standard cytotoxic chemotherapeutic agents induce dynamic changes in leukemia surface CXCR4 expression, and that chemotherapy-induced upregulation of CXCR4 represents a mechanism of acquired therapeutic resistance. Here, it was shown that cell lines variably upregulate CXCR4 with chemotherapy treatment. Those that showed upregulation were differentially protected from chemotherapy-induced apoptosis when cocultured with stroma. The functional effects of chemotherapy-induced CXCR4 upregulation in an AML cell line (MOLM-14, which harbors consistent upregulated CXCR4) and clinical specimens were explored. Importantly, enhanced stromal-cell derived factor-1α (SDF1A/CXCL12)-mediated chemotaxis and stromal protection from additional chemotherapy-induced apoptosis was found. Furthermore, treatment with plerixafor, a CXCR4 inhibitor, preferentially decreased stromal protection with higher chemotherapy-induced upregulation of surface CXCR4. Thus, increased chemokine receptor CXCR4 expression after treatment with conventional chemotherapy may represent a mechanism of therapeutic resistance in pediatric AML. IMPLICATIONS: CXCR4 may be a biomarker for the stratification and optimal treatment of patients using CXCR4 inhibitors.
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