ArticleThe Journal of experimental medicine2001
Role of promyelocytic leukemia (PML) protein in tumor suppression.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Identification of ferroptosis-genes associated with pediatric inflammatory bowel disease bioinformatics and machine learning approaches.Frontiers in immunology · 2025Article
- Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.Cold Spring Harbor perspectives in medicine · 2024Review
- Clinicopathologic features and genomic profiling of female axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary.Journal of cancer research and clinical oncology · 2024Article
- History of Developing Acute Promyelocytic Leukemia Treatment and Role of Promyelocytic Leukemia Bodies.Cancers · 2024Review
- The PML hub: An emerging actor of leukemia therapies.The Journal of experimental medicine · 2023Article
- The Sweet Side of HIPK2.Cancers · 2023Review
- N7-methylguanosine modification: from regulatory roles to therapeutic implications in cancer.American journal of cancer research · 2023Review
- The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells.International journal of molecular sciences · 2022Review
- A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer: Results from the Breast and Prostate Cancer Cohort Consortium.International journal of cancer · 2018Article
- Article
- Tumor-Suppressor Functions of the TP53 Pathway.Cold Spring Harbor perspectives in medicine · 2016Review
- HO-1, RET and PML as possible markers for risk stratification of acute myelocytic leukemia and prognostic evaluation.Oncology letters · 2015Article
- The function, regulation and therapeutic implications of the tumor suppressor protein, PML.Cell & bioscience · 2015Review
- Transcriptional repression of CDKN2D by PML/RARα contributes to the altered proliferation and differentiation block of acute promyelocytic leukemia cells.Cell death & disease · 2014Article
- The tumor suppressor PML specifically accumulates at RPA/Rad51-containing DNA damage repair foci but is nonessential for DNA damage-induced fibroblast senescence.Molecular and cellular biology · 2014Article
- Unravelling mechanisms of p53-mediated tumour suppression.Nature reviews. Cancer · 2014Article
- Targeting survival pathways in chronic myeloid leukaemia stem cells.British journal of pharmacology · 2013Review
- Loss of PML cooperates with mutant p53 to drive more aggressive cancers in a gender-dependent manner.Cell cycle (Georgetown, Tex.) · 2013Article
- Activation of protein kinase CK2 attenuates FOXO3a functioning in a PML-dependent manner: implications in human prostate cancer.Cell death & disease · 2013Article
- PML Degradation: Multiple Ways to Eliminate PML.Frontiers in oncology · 2013Article
5 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor alpha (RARalpha) gene in the vast majority of acute promyelocytic leukemia (APL) patients as a consequence of chromosomal translocations. The PMLRARalpha oncoprotein is thought to antagonize the function of PML through its ability to heterodimerize with and delocalize PML from the nuclear body. In APL, this may be facilitated by the reduction to heterozygosity of the normal PML allele. To determine whether PML acts as a tumor suppressor in vivo and what the consequences of deregulated programmed cell death in leukemia and epithelial cancer pathogenesis are, we crossed PML(-/-) mice with human cathepsin G (hCG)-PMLRARalpha or mammary tumor virus (MMTV)/neu transgenic mice (TM), models of leukemia and breast cancer, respectively. The progressive reduction of the dose of PML resulted in a dramatic increase in the incidence of leukemia, and in an acceleration of leukemia onset in PMLRARalpha TM. By contrast, PML inactivation did not affect neu-induced tumorigenesis. In hemopoietic cells from PMLRARalpha TM, PML inactivation resulted in impaired response to differentiating agents such as RA and vitamin D3 as well as in a marked survival advantage upon proapoptotic stimuli. These results demonstrate that: (a) PML acts in vivo as a tumor suppressor by rendering the cells resistant to proapoptotic and differentiating stimuli; (b) PML haploinsufficiency and the functional impairment of PML by PMLRARalpha are critical events in APL pathogenesis; and (c) aberrant control of programmed cell death plays a differential role in solid tumor and leukemia pathogenesis.
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