ArticleLeukemia2023
Microenvironmental CXCL12 deletion enhances Flt3-ITD acute myeloid leukemia stem cell response to therapy by reducing p38 MAPK signaling.
Article in Leukemia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- FGF18 mediates fibroblast-leukemia cross talk to promote acute myeloid leukemia progression.Blood · 2026Article
- Targeting BMP and TAZ/TEAD mechanotransduction pathways impairs acute myeloid leukemia chemoresistance.Leukemia · 2026Article
- Dual FLT3/MAPK14 Proteolysis-Targeting Chimera (PROTAC) Induces Potent Acute Myeloid Leukemia Cell Death.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Review
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- RPL5 deficiency-induced ribosomal stress targets a select subset of proteins and inhibits the PI3K-Akt-mTOR signaling pathway to eradicate leukemia stem cells.Cell death & disease · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- Multi-omics integration reveals immune hallmarks and biomarkers associated with FLT3 inhibitor sensitivity in FLT3-mutated AML.Blood science (Baltimore, Md.) · 2025Article
- MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway.Experimental hematology & oncology · 2025Article
- MiR-133 promotes the multidrug resistance of acute myeloid leukemia cells (HL-60/ADR) to daunorubicin.Cytotechnology · 2024Article
- Concomitant targeting of FLT3 and SPHK1 exerts synergistic cytotoxicity in FLT3-ITDCell communication and signaling : CCS · 2024Article
- Pharmacological p38 MAPK inhibitor SB203580 enhances AML stem cell line KG1a chemosensitivity to daunorubicin by promoting late apoptosis, cell growth arrest in S-phase, and miR-328-3p upregulation.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells.Biomedicines · 2023Review
- Comparison of Quantitative Mass Spectrometric Methods for Drug Target Identification by Thermal Proteome Profiling.Journal of proteome research · 2023Article
- HMGB3 promotes the malignant phenotypes and stemness of epithelial ovarian cancer through the MAPK/ERK signaling pathway.Cell communication and signaling : CCS · 2023Article
- The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Fms-like tyrosine kinase 3 (Flt3) tyrosine kinase inhibitors (Flt3-TKI) have improved outcomes for patients with Flt3-mutated acute myeloid leukemia (AML) but are limited by resistance and relapse, indicating persistence of leukemia stem cells (LSC). Here utilizing a Flt3-internal tandem duplication (Flt3-ITD) and Tet2-deleted AML genetic mouse model we determined that FLT3-ITD AML LSC were enriched within the primitive ST-HSC population. FLT3-ITD LSC showed increased expression of the CXCL12 receptor CXCR4. CXCL12-abundant reticular (CAR) cells were increased in Flt3-ITD AML marrow. CXCL12 deletion from the microenvironment enhanced targeting of AML cells by Flt3-TKI plus chemotherapy treatment, including enhanced LSC targeting. Both treatment and CXCL12 deletion partially reduced p38 mitogen-activated protein kinase (p38) signaling in AML cells and further reduction was seen after treatment in CXCL12 deleted mice. p38 inhibition reduced CXCL12-dependent and -independent maintenance of both murine and human Flt3-ITD AML LSC by MSC and enhanced their sensitivity to treatment. p38 inhibition in combination with chemotherapy plus TKI treatment leads to greater depletion of Flt3-ITD AML LSC compared with CXCL12 deletion. Our studies support roles for CXCL12 and p38 signaling in microenvironmental protection of AML LSC and provide a rationale for inhibiting p38 signaling to enhance Flt3-ITD AML targeting.
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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.