ArticleBlood advances2017
High CD123 levels enhance proliferation in response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- The E3 ubiquitin ligase Cul5 regulates hematopoietic stem cell function for steady-state hematopoiesis in mice.The Journal of clinical investigation · 2025Article
- The bispecific innate cell engager AFM28 eliminates CD123Nature communications · 2025Article
- A novel cytotoxic anti-B7-H3 affibody with therapeutic potential in acute myeloid leukemia.Frontiers in pharmacology · 2025Article
- Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges.Cancers · 2024Review
- EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.Cell communication and signaling : CCS · 2024Article
- Signaling pathways governing the behaviors of leukemia stem cells.Genes & diseases · 2024Review
- IL-3: key orchestrator of inflammation.Frontiers in immunology · 2024Review
- Biomarkers as targets for CAR-T/NK cell therapy in AML.Biomarker research · 2023Review
- CD123 a Therapeutic Target for Acute Myeloid Leukemia and Blastic Plasmocytoid Dendritic Neoplasm.International journal of molecular sciences · 2023Review
- MARCH3 negatively regulates IL-3-triggered inflammatory response by mediating K48-linked polyubiquitination and degradation of IL-3Rα.Signal transduction and targeted therapy · 2022Article
- CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Article
- Characteristics of leukemic stem cells in acute leukemia and potential targeted therapies for their specific eradication.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- CD123 Is Consistently Expressed onCancers · 2021Article
- Immunotherapy in Acute Myeloid Leukemia: Where We Stand.Frontiers in oncology · 2021Review
- Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes.Frontiers in oncology · 2021Review
- CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies.Cancers · 2020Review
- 41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo.Journal for immunotherapy of cancer · 2020Article
- Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies.Frontiers in immunology · 2020Review
- Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey (Frontiers in aging neuroscience · 2020Article
- Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow.Molecular therapy oncolytics · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High expression of the α chain of the interleukin-3 receptor (IL-3Rα; CD123) is a hallmark of acute myeloid leukemia (AML) leukemic stem cells (LSCs). Elevated CD123 expression is part of the diagnostic immunophenotyping of myeloid leukemia, and higher expression is associated with poor prognosis. However, the biological basis of the poorer prognosis is unclear, and may include heightened IL-3 signaling and non-cell autonomous interactions with the bone marrow (BM) microenvironment. We used TF-1 cells expressing different levels of CD123 and found elevated CD123 levels amplified the proliferative response to exogenous IL-3 and maintained viability in reducing IL-3 concentrations. This was associated with stronger activation of STAT5, Akt, and extracellular signal-regulated kinase 1/2 in vitro. Surprisingly, in vivo e14.5 fetal liver cells transduced with retroviral constructs to express high CD123 failed to engraft in syngeneic recipients. In exploring the underlying mechanism for this, we found that CXCR4, a key molecule involved in LSC/BM interactions, was specifically downregulated in CD123 overexpressing cells in a manner dependent on IL-3 signaling. CXCR4 downregulation was sufficient to alter the chemotactic response of hematopoietic cells to stromal derived factor-1 (SDF-1). Thus, we propose that the overexpression of CD123 in AML LSC dictates their location by altering CXCR4/SDF-1 interaction in the BM, raising the possibility that this mechanism underpins the egress of BM AML LSC and more mature cells into the circulation.
Identifiers
What OpenQuestion holds
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.