ArticleJournal of hematology & oncology2016
Immunoprofiling of leukemic stem cells CD34+/CD38-/CD123+ delineate FLT3/ITD-positive clones.
Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics.Frontiers in oncology · 2020Pooled it
- Impact of CD123 expression, analyzed by immunohistochemistry, on clinical outcomes in patients with acute myeloid leukemia.International journal of hematology · 2019Trial
- Measurable Residual Disease.Methods in molecular biology (Clifton, N.J.) · 2027Article
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- Regulating Ferroptosis in Leukemic Stem Cells: From Stemness Preservation to Targeted Differentiation Strategies.Stem cell reviews and reports · 2026Review
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- Src inhibition potentiates MCL-1 antagonist activity in acute myeloid leukemia.Signal transduction and targeted therapy · 2025Article
- Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.Cancer immunology, immunotherapy : CII · 2024Article
- Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia.Annals of hematology · 2024Review
- Characterization of stem cell landscape and assessing the stemness degree to aid clinical therapeutics in hematologic malignancies.Scientific reports · 2024Article
- EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.Cell communication and signaling : CCS · 2024Article
- Shift of N-MYC Oncogene Expression in AML Patients Carrying the FLT3-ITD Mutation.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Article
- IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML.Blood advances · 2023Article
- CD123 a Therapeutic Target for Acute Myeloid Leukemia and Blastic Plasmocytoid Dendritic Neoplasm.International journal of molecular sciences · 2023Review
- Multiparameter flow cytometry in the evaluation of myelodysplasia: Analytical issues: Recommendations from the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group.Cytometry. Part B, Clinical cytometry · 2023Review
- MDM2 antagonist improves therapeutic activity of azacitidine in myelodysplastic syndromes and chronic myelomonocytic leukemia.Leukemia & lymphoma · 2022Article
- Review
- Hematological indices reference intervals for a healthy Arab population in Qatar: Effect of age, gender, and geographic location.Medicine · 2022Article
- Human acute myeloid leukemia stem cells: evolution of concept.Blood research · 2022Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute myeloid leukemia (AML) is a heterogeneous clonal disorder presenting with accumulation of proliferating undifferentiated blasts. Xenograft transplantation studies have demonstrated a rare population of leukemia-initiating cells called leukemic stem cells (LSCs) capable of propagating leukemia that are enriched in the CD34+/CD38- fraction. LSCs are quiescent, resistant to chemotherapy and likely responsible for relapse and therefore represent an ideal target for effective therapy. LSCs are reported to overexpress the alpha subunit of the IL-3 receptor (CD123) compared to normal CD34+/CD38- hematopoietic stem cells. It has not been demonstrated whether CD123-positive (CD34+/CD38-) subpopulation is enriched for any clonal markers of AML or any LSC properties. The aims of this study were to investigate whether FMS-like tyrosine kinase (FLT3)/internal tandem duplication (ITD) mutations are present at LSC level and whether FLT3/ITD mutation is confined to LSC as defined by CD34+/CD38-/CD123+ and not CD34+/CD38-/CD123-.
methodsThirty-four AML cases were analyzed by five-color flow cytometry and sequential gating strategy to characterize of CD34+/CD38-/CD123+ cells. These cells were sorted, analyzed by PCR, and sequenced for FLT3/ITD.
resultsIn this study, we confirm significant expression of CD123 in 32/34 cases in the total blast population (median expression = 86 %). CD123 was also expressed in the CD34+/CD38- cells (96 ± 2 % positive) from 28/32 for CD123+ AML. CD123 was not expressed/low in normal bone marrow CD34+/CD38- cells (median expression = 0 %, range (0-.004 %). AML samples were tested for FLT3/ITD (10 positive/25). FLT3/ITD+ AML cases were sorted into two putative LSC populations according to the expression of CD123 and analyzed for FLT3/ITD again in the stem cell fractions CD34+/CD38-/CD123+ and CD34+/CD38-/CD123-. Interestingly, FLT3/ITD was only detected in CD34+/CD38-/CD123+ (7/7) and not in CD34+/CD38-/CD123- subpopulation (6/7).
conclusionsThis finding shows that FLT3/ITD are present at LSC level and may be a primary and not secondary event in leukemogenesis, and the oncogenic events of FLT3/ITD happen at a cell stage possessing CD123. It shows that CD123 immunoprofiling provides further delineation of FLT3+ LSC clone. This novel finding provides a rationale for treatment involving CD123-targeting antibodies with intracellular FLT3 inhibitors directed against CD34+/CD38-/CD123+. This may result in more effective anti-LSC eradication.
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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.