ArticleLeukemia2012
Src inhibitors, PP2 and dasatinib, increase retinoic acid-induced association of Lyn and c-Raf (S259) and enhance MAPK-dependent differentiation of myeloid leukemia cells.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
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- Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- FGR Src family kinase causes signaling and phenotypic shift mimicking retinoic acid-induced differentiation of leukemic cells.Oncotarget · 2025Article
- Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells.Frontiers in immunology · 2025Article
- Combination of midostaurin and ATRA exerts dose-dependent dual effects on acute myeloid leukemia cells with wild type FLT3.BMC cancer · 2022Article
- The dual role of CD6 as a therapeutic target in cancer and autoimmune disease.Frontiers in medicine · 2022Review
- Evidence of off-target effects of bosutinib that promote retinoic acid-induced differentiation of non-APL AML cells.Cell cycle (Georgetown, Tex.) · 2021Article
- Role for Fgr and Numb in retinoic acid-induced differentiation and G0 arrest of non-APL AML cells.Oncotarget · 2021Article
- Salt-inducible kinase inhibition sensitizes human acute myeloid leukemia cells to all-trans retinoic acid-induced differentiation.International journal of hematology · 2021Article
- Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.Exploration of targeted anti-tumor therapy · 2021Review
- Dissecting the novel partners of nuclear c-Raf and its role in all-trans retinoic acid (ATRA)-induced myeloblastic leukemia cells differentiation.Experimental cell research · 2020Article
- Depleting interferon regulatory factor-1(IRF-1) with CRISPR/Cas9 attenuates inducible oxidative metabolism without affecting RA-induced differentiation in HL-60 human AML cells.FASEB bioAdvances · 2020Article
- Roscovitine enhances all-Oncotarget · 2020Article
- Enzastaurin enhances ATRA-induced differentiation of acute myeloid leukemia cells.American journal of translational research · 2020Article
- Retinoic acid and 6-formylindolo(3,2-b)carbazole (FICZ) combination therapy reveals putative targets for enhancing response in non-APL AML.Leukemia & lymphoma · 2019Article
- SHP1 and SHP2 inhibition enhances the pro-differentiative effect of phorbol esters: an alternative approach against acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2019Article
- Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells.Leukemia & lymphoma · 2018Article
- CXCR5 overexpression in HL-60 cells enhances chemotaxis toward CXCL13 without anticipated interaction partners or enhanced MAPK signaling.In vitro cellular & developmental biology. Animal · 2018Article
- A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia.Leukemia & lymphoma · 2018Article
- Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.Molecular cancer · 2018Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
All-trans-retinoic-acid (ATRA)-induced differentiation of human myeloid leukemia cells is characterized by persistent mitogen-activated protein kinase (MAPK) signaling. Fragmentary data suggests Src family kinase (SFK) inhibitors enhance differentiation, and thus have potential therapeutic value. The present study shows that SFK inhibitors PP2 and dasatinib enhance aspects of MAPK signaling and regulate a panel of differentiation markers, including CD11b and p47(phox). HL-60 and NB4 myeloid leukemia cells show accelerated ATRA-induced G1/0 arrest/differentiation with inhibitor co-treatment. We also identified components of a Lyn- and c-Raf-containing MAPK signaling complex augmented by the inhibitors. PP2 and dasatinib increased the ATRA-induced expression of Lyn and c-Raf (total and c-RafpS259) and their interaction. The Lyn-associated serine/threonine kinase, casein kinase II (CK2), also complexed with c-Raf and c-RafpS259, and the kinase suppressor of Ras 1 (KSR1) scaffold protein bound c-Raf, Lyn and extracellular signal-regulated kinase (ERK). c-Raf/ERK association was increased by the inhibitors, which is significant as ERK may cause c-Raf C-terminal domain (CTD) phosphorylation in a putative feedback mechanism. Consistent with this, inhibitor treatment caused more CTD phosphorylation. Lyn knockdown decreased c-Raf CTD and S259 phosphorylation. This is the first evidence suggesting SFK inhibitors enhance ATRA-induced differentiation through a possible feedback loop involving KSR1-scaffolded c-Raf and ERK complexed with Lyn and CK2.
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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.