ArticleLeukemia2015
Lithium chloride antileukemic activity in acute promyelocytic leukemia is GSK-3 and MEK/ERK dependent.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Angptl5 restricts primitive hematopoiesis by promoting retinoic acid signaling in zebrafish.PLoS biology · 2026Article
- Therapy-related myeloid neoplasms following curative treatment of acute promyelocytic leukemia: incidence, correlation with therapeutic regimen, and future directions.Journal of hematopathology · 2024Article
- Lithium in Cancer Therapy: Friend or Foe?Cancers · 2023Review
- GSK-3: a multifaceted player in acute leukemias.Leukemia · 2021Review
- Evolving Chemotherapy Free Regimens for Acute Promyelocytic Leukemia.Frontiers in oncology · 2021Review
- Targeting ERK-Hippo Interplay in Cancer Therapy.International journal of molecular sciences · 2020Review
- MEK2 Negatively Regulates Lipopolysaccharide-Mediated IL-1β Production through HIF-1α Expression.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- The effect of lithium on the progression-free and overall survival in patients with metastatic differentiated thyroid cancer undergoing radioactive iodine therapy.Clinical endocrinology · 2018Article
- Lithium Reversibly Inhibits Schwann Cell Proliferation and Differentiation Without Inducing Myelin Loss.Molecular neurobiology · 2017Article
- Lithium Chloride Facilitates Autophagy Following Spinal Cord Injury via ERK-dependent Pathway.Neurotoxicity research · 2017Article
- Effect of ATRA and ATO on the expression of tissue factor in NB4 acute promyelocytic leukemia cells and regulatory function of the inflammatory cytokines TNF and IL-1β.Annals of hematology · 2017Article
- pVAX14DNA-mediated add-on immunotherapy combined with arsenic trioxide and all-trans retinoic acid targeted therapy effectively increases the survival of acute promyelocytic leukemia mice.Blood cancer journal · 2015Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently identified that the MEK/ERK1/2 pathway synergized with retinoic acid (RA) to restore both transcriptional activity and RA-induced differentiation in RA-resistant acute promyelocytic leukemia (APL) cells. To target the MEK/ERK pathway, we identified glycogen synthase kinase-3β (GSK-3β) inhibitors including lithium chloride (LiCl) as activators of this pathway in APL cells. Using NB4 (RA-sensitive) and UF-1 (RA-resistant) APL cell lines, we observed that LiCl as well as synthetic GSK-3β inhibitors decreased proliferation, induced apoptosis and restored, in RA-resistant cells, the expression of RA target genes and the RA-induced differentiation. Inhibition of the MEK/ERK1/2 pathway abolished these effects. These results were corroborated in primary APL patient cells and translated in vivo using an APL preclinical mouse model in which LiCl given alone was as efficient as RA in increasing survival of leukemic mice compared with untreated mice. When LiCl was combined with RA, we observed a significant survival advantage compared with mice treated by RA alone. In this work, we demonstrate that LiCl, a well-tolerated agent in humans, has antileukemic activity in APL and that it has the potential to restore RA-induced transcriptional activation and differentiation in RA-resistant APL cells in an MEK/ERK-dependent manner.
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