ArticleCancer science2015
Preclinical activity of the novel B-cell-specific Moloney murine leukemia virus integration site 1 inhibitor PTC-209 in acute myeloid leukemia: Implications for leukemia therapy.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Progressive Dynamics of Cancer Stem Cells in Oral Squamous Cell Carcinoma.Current cancer drug targets · 2025Article
- Targeting cancer stemness mediated by BMI1 and MCL1 for non-small cell lung cancer treatment.Journal of cellular and molecular medicine · 2022Article
- The Crucial Roles of Bmi-1 in Cancer: Implications in Pathogenesis, Metastasis, Drug Resistance, and Targeted Therapies.International journal of molecular sciences · 2022Review
- Small-molecule inhibitors targeting Polycomb repressive complex 1 RING domain.Nature chemical biology · 2021Article
- Article
- The Prognostic Significance of the BMI-1 and BAALC Genes in Adult Patients with Acute Myeloid Leukemia.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2020Article
- Chromatin regulatory mechanisms and therapeutic opportunities in cancer.Nature cell biology · 2019Review
- Polycomb complexes in normal and malignant hematopoiesis.The Journal of cell biology · 2019Review
- PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation.Frontiers in pharmacology · 2019Article
- Synthesis of Cyanoenone-Modified Diterpenoid Analogs as Novel Bmi-1-Mediated Antitumor Agents.ACS medicinal chemistry letters · 2018Article
- Targeting of BMI-1 expression by the novel small molecule PTC596 in mantle cell lymphoma.Oncotarget · 2018Article
- Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes.Oncotarget · 2017Article
- Synthesis and Characterization of Novel BMI1 Inhibitors Targeting Cellular Self-Renewal in Hepatocellular Carcinoma.Targeted oncology · 2017Article
- The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells.Blood cancer journal · 2017Article
- Bmi-1 serves as a potential novel marker for progression in human cutaneous basal cell carcinoma.International journal of clinical and experimental pathology · 2017Article
- Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma.Cancer cell international · 2017Article
- Targeting of BMI-1 with PTC-209 shows potent anti-myeloma activity and impairs the tumour microenvironment.Journal of hematology & oncology · 2016Article
- Knockdown of Sall4 inhibits intrahepatic cholangiocarcinoma cell migration and invasion in ICC-9810 cells.OncoTargets and therapy · 2016Article
- Preclinical activity of the novel B-cell-specific Moloney murine leukemia virus integration site 1 inhibitor PTC-209 in acute myeloid leukemia: Implications for leukemia therapy.Cancer science · 2015Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Curing patients with acute myeloid leukemia (AML) remains a therapeutic challenge. The polycomb complex protein B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of leukemia stem cells. We investigated the prognostic significance of BMI-1 in AML and the effects of a novel small molecule selective inhibitor of BMI-1, PTC-209. BMI-1 protein expression was determined in 511 newly diagnosed AML patients together with 207 other proteins using reverse-phase protein array technology. Patients with unfavorable cytogenetics according to Southwest Oncology Group criteria had higher levels of BMI-1 compared to those with favorable (P = 0.0006) or intermediate cytogenetics (P = 0.0061), and patients with higher levels of BMI-1 had worse overall survival (55.3 weeks vs. 42.8 weeks, P = 0.046). Treatment with PTC-209 reduced protein level of BMI-1 and its downstream target mono-ubiquitinated histone H2A and triggered several molecular events consistent with the induction of apoptosis, this is, loss of mitochondrial membrane potential, caspase-3 cleavage, BAX activation, and phosphatidylserine externalization. PTC-209 induced apoptosis in patient-derived CD34(+)CD38(low/-) AML cells and, less prominently, in CD34(-) differentiated AML cells. BMI-1 reduction by PTC-209 directly correlated with apoptosis induction in CD34(+) primary AML cells (r = 0.71, P = 0.022). However, basal BMI-1 expression was not a determinant of AML sensitivity. BMI-1 inhibition, which targets a primitive AML cell population, might offer a novel therapeutic strategy for AML.
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