ReviewStem cells translational medicine2014
Kinase-independent mechanisms of resistance of leukemia stem cells to tyrosine kinase inhibitors.
Review in Stem cells translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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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
18 citing papers in PubMed, 35 citations in OpenAlex.
- The value of protein allostery in rational anticancer drug design: an update.Expert opinion on drug discovery · 2024Review
- EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis.Communications biology · 2023Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Recent Advances in PROTACs for Drug Targeted Protein Research.International journal of molecular sciences · 2022Review
- 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
- Imatinib can act as an Allosteric Activator of Abl Kinase.Journal of molecular biology · 2022Article
- Design, synthesis, and biological evaluation of Bcr-Abl PROTACs to overcome T315I mutation.Acta pharmaceutica Sinica. B · 2021Article
- PROTACs to address the challenges facing small molecule inhibitors.European journal of medicinal chemistry · 2021Review
- Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies.Journal of hematology & oncology · 2020Review
- Identification of leukemia stem cell expression signatures through Monte Carlo feature selection strategy and support vector machine.Cancer gene therapy · 2020Article
- Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation.Cancer research · 2019Article
- BCL2 inhibitor ABT-199 and JNK inhibitor SP600125 exhibit synergistic cytotoxicity against imatinib-resistant Ph+ ALL cells.Biochemistry and biophysics reports · 2018Article
- Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib.Cancer medicine · 2017Article
- BCR-ABL1-induced downregulation of WASP in chronic myeloid leukemia involves epigenetic modification and contributes to malignancy.Cell death & disease · 2017Article
- Oridonin Triggers Chaperon-mediated Proteasomal Degradation of BCR-ABL in Leukemia.Scientific reports · 2017Article
- Article
- Detection approaches for multidrug resistance genes of leukemia.Drug design, development and therapy · 2017Review
- Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL.Angewandte Chemie (International ed. in English) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors such as imatinib mesylate have changed the clinical course of chronic myeloid leukemia; however, the observation that these inhibitors do not target the leukemia stem cell implies that patients need to maintain lifelong therapy. The mechanism of this phenomenon is unclear: the question of whether tyrosine kinase inhibitors are inactive inside leukemia stem cells or whether leukemia stem cells do not require breakpoint cluster region (Bcr)-Abl signaling is currently under debate. Herein, I propose an alternative model: perhaps the leukemia stem cell requires Bcr-Abl, but is dependent on its kinase-independent functions. Kinases such as epidermal growth factor receptor and Janus kinase 2 possess kinase-independent roles in regulation of gene expression; it is worth investigating whether Bcr-Abl has similar functions. Mechanistically, Bcr-Abl is able to activate the Ras, phosphatidylinositol 3-kinase/Akt, and/or the Src-kinase Hck/Stat5 pathways in a scaffolding-dependent manner. Whereas the scaffolding activity of Bcr-Abl with Grb2 is dependent on autophosphorylation, kinases such as Hck can use Bcr-Abl as substrate, inducing phosphorylation of Y177 to enable scaffolding ability in the absence of Bcr-Abl catalytic activity. It is worth investigating whether leukemia stem cells exclusively express kinases that are able to use Bcr-Abl as substrate. A kinase-independent role for Bcr-Abl in leukemia stem cells would imply that drugs that target Bcr-Abl's scaffolding ability or its DNA-binding ability should be used in conjunction with current therapeutic regimens to increase their efficacy and eradicate the stem cells of chronic myeloid leukemia.
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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.