ArticleLeukemia2001
The JAK2 inhibitor AG490 predominantly abrogates the growth of human B-precursor leukemic cells with 11q23 translocation or Philadelphia chromosome.
Article in Leukemia, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 56 citations in OpenAlex.
- WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target.Journal of translational medicine · 2020Article
- Targeting STAT3 signaling in kidney disease.American journal of physiology. Renal physiology · 2019Review
- Molecular processes involved in B cell acute lymphoblastic leukaemia.Cellular and molecular life sciences : CMLS · 2018Review
- Role of ZNF224 in c-Myc repression and imatinib responsiveness in chronic myeloid leukemia.Oncotarget · 2018Article
- Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells.BMC cancer · 2017Article
- MYC Deregulation in Primary Human Cancers.Genes · 2017Review
- Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition.Leukemia · 2017Review
- Mitochondrial Stat3, the Need for Design Thinking.International journal of biological sciences · 2016Review
- Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma.Oncoimmunology · 2013Article
- The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death.Cell death & disease · 2013Article
- BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia.Nature chemical biology · 2012Article
- Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis.PloS one · 2012Article
- AHI-1: a novel signaling protein and potential therapeutic target in human leukemia and brain disorders.Oncotarget · 2011Review
- The small molecule, LLL12, inhibits STAT3 phosphorylation and induces apoptosis in medulloblastoma and glioblastoma cells.PloS one · 2011Article
- Janus Kinase 2 Inhibitor AG490 Inhibits the STAT3 Signaling Pathway by Suppressing Protein Translation of gp130.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2009Article
- Article
- Jak2 inhibitors: rationale and role as therapeutic agents in hematologic malignancies.Current oncology reports · 2009Review
- AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells.The Journal of experimental medicine · 2008Article
- Article
- Jak2 is involved in c-Myc induction by Bcr-Abl.Oncogene · 2002Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Janus kinase (JAK) family is one of intracellular protein tyrosine kinases (PTKs) present in hematopoietic and lymphoid cells and has been shown to play a crucial role in a variety of biological responses. It was reported that a human B-precursor leukemic cell line was potently inhibited in its proliferation by one of synthetic PTK inhibitors (tyrphostins), AG490, via anti-JAK2 activity. However, no extensive studies about it have been performed. In the present study, we tested 16 human lymphoid leukemic cell lines (B-precursor, 12; T cell, four) for their sensitivity to AG490 using 3H-thymidine incorporation and colony formation assays, and found that B-precursor cell lines with 11q23 translocation or Philadelphia chromosome (Ph1) whose JAK2 proved to be constitutively phosphorylated were predominantly sensitive to AG490 at a concentration that has few inhibitory effect on normal hematopoiesis. We first revealed the association of JAK2 with BCR-ABL in Ph1-positive cell lines and with Bruton's tyrosine kinase (BTK) in cell lines with 11q23 translocation by coimmunoprecipitation experiments. Of interest, AG490 markedly down-regulated phosphorylation of JAK2, but rather transiently up-regulated phosphorylation of BCR-ABL and BTK, suggesting direct implication of AG490 in the process of the JAK2 dephosphorylation. These results indicate that AG490 exerts a potent inhibitory activity to B-precursor leukemia with specific chromosomal abnormalities, and a therapeutic approach using AG490 is expected.
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