ArticleLeukemia2008
Enhanced BCR-ABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth suppression in CML progenitors.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 107 citations in OpenAlex.
- Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study.European journal of haematology · 2021Trial
- Targeting leukemic stem and progenitor cells expressing different BCR::ABL1 levels: antileukemic activity of asciminib with or without TKIs.Frontiers in pharmacology · 2026Article
- HighOncoTargets and therapy · 2023Article
- Impact of metformin on tyrosine kinase inhibitor response in chronic myeloid leukemia.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2022Observational
- Polo-like kinase-1, Aurora kinase A and WEE1 kinase are promising druggable targets in CML cells displaying BCR::ABL1-independent resistance to tyrosine kinase inhibitors.Frontiers in oncology · 2022Article
- Combined Inhibition of Bcl2 and Bcr-Abl1 Exercises Anti-Leukemia Activity but Does Not Eradicate the Primitive Leukemic Cells.Journal of clinical medicine · 2021Article
- Inference of kinase-signaling networks in human myeloid cell line models by Phosphoproteomics using kinase activity enrichment analysis (KAEA).BMC cancer · 2021Article
- Impact of the Breakpoint Region on the Leukemogenic Potential and the TKI Responsiveness of AtypicalFrontiers in pharmacology · 2021Article
- BCR-ABL tyrosine kinase inhibitors promote pathological changes in dilator phenotype in the human microvasculature.Microcirculation (New York, N.Y. : 1994) · 2020Article
- Chronic myeloid leukemia stem cells require cell-autonomous pleiotrophin signaling.The Journal of clinical investigation · 2020Article
- Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells.Frontiers in cell and developmental biology · 2020Review
- Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation.Cancer research · 2019Article
- Adhesion structures in leukemia cells and their regulation by Src family kinases.Cell adhesion & migration · 2018Article
- Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia.Molecular oncology · 2018Article
- Article
- Knowledge-guided gene prioritization reveals new insights into the mechanisms of chemoresistance.Genome biology · 2017Article
- Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration.The Journal of clinical investigation · 2016Article
- Article
- A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression.The Journal of experimental medicine · 2015Article
- Antitumoral effects of cyclin-dependent kinases inhibitors CR8 and MR4 on chronic myeloid leukemia cell lines.Journal of biomedical science · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The therapeutic success of imatinib in chronic myeloid leukemia (CML) is hampered by persistence of malignant stem cells. We investigated whether nilotinib, a more potent BCR-ABL kinase inhibitor could target CML primitive progenitors more effectively than imatinib. CML and normal progenitor cells were cultured with nilotinib or imatinib in growth factor supplemented medium. Nilotinib inhibited BCR-ABL kinase activity at lower concentrations than imatinib. Nilotinib inhibited mitogen-activated protein kinase (MAPK), AKT and STAT5 phosphorylation in CML CD34(+) cells in the absence of growth factors (GFs), but did not suppress AKT and STAT5 activity, and resulted in increased MAPK activity, in the presence of GFs. Nilotinib and imatinib resulted in similar suppression of CML primitive and committed progenitors in long-term culture-initiating cell and colony-forming cell assays. Inhibition of progenitor growth was related to marked reduction in proliferation, but only a modest increase in apoptosis. Nilotinib did not show increased efficacy in reducing nondividing CML progenitors compared with imatinib. These results indicate that more potent tyrosine kinase inhibitors by themselves will not be more effective in eliminating CML progenitors than imatinib and that additional mechanism required for maintenance of malignant stem cells need to be identified to improve targeting of leukemia stem cells.
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.