ArticleLeukemia2010
Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin.
Article in Leukemia, 2010. 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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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Rapamycin and Niacin combination induces apoptosis and cell cycle arrest through autophagy activation on acute myeloid leukemia cells.Molecular biology reports · 2024Article
- Activation of Autophagy Ameliorates Age-Related Neurogenesis Decline and Neurodysfunction in Adult Mice.Stem cell reviews and reports · 2022Article
- Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia.Antioxidants (Basel, Switzerland) · 2021Article
- Pharmacological Inhibition of Oncogenic STAT3 and STAT5 Signaling in Hematopoietic Cancers.Cancers · 2020Review
- Imipramine blue sensitively and selectively targets FLT3-ITD positive acute myeloid leukemia cells.Scientific reports · 2017Article
- eIF4B is a convergent target and critical effector of oncogenic Pim and PI3K/Akt/mTOR signaling pathways in Abl transformants.Oncotarget · 2016Article
- Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells.Cancers · 2015Article
- BCL6 controls Th9 cell development by repressing Il9 transcription.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Regulation of the interferon regulatory factor-8 (IRF-8) tumor suppressor gene by the signal transducer and activator of transcription 5 (STAT5) transcription factor in chronic myeloid leukemia.The Journal of biological chemistry · 2014Article
- Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy.Haematologica · 2014Review
- PI3K inhibitor GDC-0941 enhances apoptotic effects of BH-3 mimetic ABT-737 in AML cells in the hypoxic bone marrow microenvironment.Journal of molecular medicine (Berlin, Germany) · 2013Article
- Oxidative metabolism in cancer: A STAT affair?JAK-STAT · 2013Review
- STAT5 acetylation: Mechanisms and consequences for immunological control and leukemogenesis.JAK-STAT · 2013Review
- Src family kinases mediate cytoplasmic retention of activated STAT5 in BCR-ABL-positive cells.Oncogene · 2013Article
- mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms.PloS one · 2013Article
- A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers.The Journal of clinical investigation · 2012Article
- Glycolysis inhibition targets Mcl-1 to restore sensitivity of lymphoma cells to ABT-737-induced apoptosis.Leukemia · 2012Article
- Janus kinase deregulation in leukemia and lymphoma.Immunity · 2012Review
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 3 countries.
Funding
Abstract
Signal transducer and activator of transcription-5 (STAT5) is a critical transcription factor for normal hematopoiesis and its sustained activation is associated with hematologic malignancy. A persistently active mutant of STAT5 (STAT5a(S711F)) associates with Grb2-associated binding protein 2 (Gab2) in myeloid leukemias and promotes growth in vitro through AKT activation. Here we have retrovirally transduced wild-type or Gab2(-/-) mouse bone marrow cells expressing STAT5a(S711F) and transplanted into irradiated recipient mice to test an in vivo myeloproliferative disease model. To target Gab2-independent AKT/mTOR activation, we treated wild-type mice separately with rapamycin. In either case, mice lacking Gab2 or treated with rapamycin showed attenuated myeloid hyperplasia and modestly improved survival, but the effects were not cytotoxic and were reversible. To improve on this approach, we combined in vitro targeting of STAT5-mediated AKT/mTOR using rapamycin with inhibition of the STAT5 direct target genes bcl-2 and bcl-X(L) using ABT-737. Striking synergy with both drugs was observed in mouse BaF3 cells expressing STAT5a(S711F), TEL-JAK2 or BCR-ABL and in the relatively single agent-resistant human BCR-ABL-positive K562 cell line. Therefore, targeting distinct STAT5-mediated survival signals, for example, bcl-2/bcl-X(L) and AKT/mTOR may be an effective therapeutic approach for human myeloproliferative neoplasms.
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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.