ArticleBlood2009
FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 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
154 citing papers in PubMed, 261 citations in OpenAlex.
- Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome.American journal of hematology · 2015Trial
- The sorafenib plus nutlin-3 combination promotes synergistic cytotoxicity in acute myeloid leukemic cells irrespectively of FLT3 and p53 status.Haematologica · 2012Trial
- Novel targeted therapy and cellular immunotherapy enabling allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute myeloid leukemia.Chinese medical journal · 2026Review
- Wired to Survive: How AML Cytogenetics Shape Apoptotic Dependence and Venetoclax Resistance.Genes · 2026Review
- Targeting FLT3 in Acute Myeloid Leukemia: Structural Insights and Key Challenges.ACS bio & med chem Au · 2026Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Dual action of pimozide through lysosome disruption and inhibition of STATs induces apoptosis in chronic lymphocytic leukemia (CLL).Blood advances · 2026Article
- Clinical Significance of FLT3-ITD Variation Allele Frequency in Acute Myeloid Leukemia: A Multicenter Study.Hematological oncology · 2026Article
- Therapeutic targeting of BCL-2 during CART cell production augments potency through non-apoptotic adaptive changes.Signal transduction and targeted therapy · 2026Article
- Comparative efficacy of different therapeutic approaches in treatment naïve FLT3-mutated AML eligible for intensive chemotherapy: a Bayesian network meta-analysis of randomized trials.Annals of hematology · 2026Article
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Targeting MCL-1 and MAPK overcomes venetoclax resistance in FLT3-ITD-positive AML cells harbouring activating PTPN11 (SHP-2) mutations.British journal of haematology · 2026Article
- FLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustion.Blood advances · 2026Article
- Review
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- Current Therapeutic Strategies for FLT3-Mutated Acute Myeloid Leukemia: A Narrative Review.Cureus · 2025Review
- Efficacy and prognostic analysis of venetoclax combined with hypomethylating agents for induction therapy in acute myeloid leukemia: a multi-center real-world study on indication-specific stratification, molecular markers, and hematologic toxicities.Cancer cell international · 2025Article
- Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era.Cancers · 2025Review
- Distinct leukemogenic mechanism of acute promyelocytic leukemia based on genomic structure of PML::RARα.Leukemia · 2025Article
- Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies.European journal of haematology · 2025Review
94 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myeloid cell leukemia-1 (MCL-1) is an essential survival factor for hematopoiesis. In humans, hematopoietic stem cells (HSCs) express MCL-1 at the highest level in response to FMS-like tyrosine kinase-3 (FLT3) signaling. We here show that this FLT3-dependent stem cell maintenance system also plays a critical role in survival of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). The CD34(+)CD38(-) LSC fraction expresses high levels of FLT3 as well as MCL-1, even compared with normal HSCs. Treatment with FLT3 ligand induced further MCL-1 up-regulation in LSCs in all AML cases tested. Interestingly, the group of samples expressing the highest levels of MCL-1 constituted AML with FLT3-internal tandem duplications (ITD). In FLT3-ITD AML cell lines, cells expressed a high level of MCL-1, and an inhibition of MCL-1 induced their apoptotic cell death. A tyrosine kinase inhibitor suppressed MCL-1 expression, and induced apoptosis that was reversed by the enforced MCL-1 expression. Finally, transduction of FLT3-ITD into HSCs strongly activated MCL-1 expression through its signal transducer and activator of transcription 5 (STAT5)-docking domains. This effect was completely abrogated when STAT5 activation was blocked. Thus, the acquisition of FLT3-ITD ensures LSC survival by up-regulating MCL-1 via constitutive STAT5 activation that is independent of wild-type FLT3 signaling.
Indexed as
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.