ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Dasatinib inhibits the growth of molecularly heterogeneous myeloid leukemias.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05042531 (Clinical Research for Azacitidine Combined With Low-dose Dasatinib in Maintenance Therapy of Acute Myeloid Leukemia), which is not on this map. Cited by 25 papers.
What it found
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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.
Clinical Research for Azacitidine Combined With Low-dose Dasatinib in Maintenance Therapy of Acute Myeloid Leukemia
Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Trial
- Article
- Evidence of off-target effects of bosutinib that promote retinoic acid-induced differentiation of non-APL AML cells.Cell cycle (Georgetown, Tex.) · 2021Article
- Proteomic Analysis of Src Family Kinase Phosphorylation States in Cancer Cells Suggests Deregulation of the Unique Domain.Molecular cancer research : MCR · 2021Article
- Article
- Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia.Haematologica · 2021Article
- Activity-Based Protein Profiling Reveals Potential Dasatinib Targets in Gastric Cancer.International journal of molecular sciences · 2020Article
- Review
- Ortho-Topolin Riboside Induced Differentiation through Inhibition of STAT3 Signaling in Acute Myeloid Leukemia HL-60 CellsTurkish journal of haematology : official journal of Turkish Society of Haematology · 2019Article
- Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells.Leukemia & lymphoma · 2018Article
- Lyn, a tyrosine kinase closely linked to the differentiation status of primary acute myeloid leukemia blasts, associates with negative regulation of all-trans retinoic acid (ATRA) and dihydroxyvitamin D3 (VD3)-induced HL-60 cells differentiation.Cancer cell international · 2016Article
- Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets.Leukemia research reports · 2016Article
- Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.International journal of oncology · 2015Article
- Hematopoietic cell kinase (HCK) as a therapeutic target in immune and cancer cells.Oncotarget · 2015Review
- Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells.PloS one · 2015Article
- Transforming growth factor β signaling overcomes dasatinib resistance in lung cancer.PloS one · 2014Article
- Dasatinib accelerates valproic acid-induced acute myeloid leukemia cell death by regulation of differentiation capacity.PloS one · 2014Article
- Article
- Src Family Kinase Inhibitor PP2 Has Different Effects on All-Trans-Retinoic Acid or Arsenic Trioxide-Induced Differentiation of an Acute Promyelocytic Leukemia Cell Line.Cancer research and treatment · 2013Article
- Dasatinib inhibits primary melanoma cell proliferation through morphology-dependent disruption of Src-ERK signaling.Oncology letters · 2013Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeDasatinib is a dual Src/Abl inhibitor recently approved for Bcr-Abl+ leukemias with resistance or intolerance to prior therapy. Because Src kinases contribute to multiple blood cell functions by triggering a variety of signaling pathways, we hypothesized that their molecular targeting might lead to growth inhibition in acute myeloid leukemia (AML). EXPERIMENTAL
designWe studied growth factor-dependent and growth factor-independent leukemic cell lines, including three cell lines expressing mutants of receptor tyrosine kinases (Flt3 or c-Kit) as well as primary AML blasts for responsiveness to dasatinib.
resultsDasatinib resulted in the inhibition of Src family kinases in all cell lines and blast cells at approximately 1 x 10(-9) mol/L. It also inhibited mutant Flt3 or Kit tyrosine phosphorylation at approximately 1 x 10(-6) mol/L. Mo7e cells expressing the activating mutation (codon 816) of c-Kit were most sensitive to growth inhibition with a GI(50) of 5 x 10(-9) mol/L. Primary AML blast cells exhibited a growth inhibition of <1 x 10(-6) mol/L. Cell lines that showed growth inhibition at approximately 1 x 10(-6) mol/L showed a G(1) cell cycle arrest and correlated with accumulation of p21 and p27 protein. The addition of rapamycin or cytotoxic agents enhanced growth inhibition. Dasatinib also caused the apoptosis of Mo7e cells expressing oncogenic Kit.
conclusionsAlthough all of the precise targets for dasatinib are not known, this multikinase inhibitor causes either growth arrest or apoptosis in molecularly heterogeneous AML. The addition of cytotoxic or targeted agents can enhance its effects.
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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.