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PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs.
CIViC holds 7 clinical evidence items and 0 assertions across 6 variants, naming Tretinoin, Arsenic Trioxide and Tamibarotene. Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes literature 0.99, affected pathway 0.87, genetic association 0.63, somatic mutation 0.80). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Lung. In OnCo, 2 product records name it (Arsenic trioxide and Tretinoin (all-trans retinoic acid, ATRA)).
In plain words · PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.
PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms.
No product in this corpus aims at PML yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 2 medicines aimed at it (Arsenic trioxide, Tretinoin (all-trans retinoic acid, ATRA)) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA PML: RNA low tissue specificity; high antibody staining in 25 normal tissues; highest cancer staining head and neck cancer (3 of 3 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Thyroid cancer, Lung cancer (all types), Skin cancer (all types), Myeloid neoplasms); Open Targets associates it with 2 specific cancer types at or above 0.5 (thyroid gland carcinoma, uterine corpus leiomyoma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas PML tissue; Open Targets ENSG00000140464 associations
First described 1991. Earliest sequence paper UniProt cites for the protein: de The et al, Cell, 1991, "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR". Source.
Sources: HGNC HGNC:9113 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P29590 (protein name, function text, keywords and locations (REST API)); CIViC gene PML (7 evidence items, 0 assertions, 6 variants; diseases: Acute Promyelocytic Leukaemia (GraphQL API, CC0)); Open Targets ENSG00000140464 (association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: thyroid cancer 0.57, skin cancer 0.53, myeloproliferative neoplasm 0.52, leukaemia 0.58 (GraphQL API, CC0)); IntOGen PML (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localisation and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. Location: Nucleus; Nucleus, nucleoplasm; Cytoplasm; Nucleus, PML body (UniProt). Locus 15q24.1 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Epididymis, Esophagus, Lung, Ovary, Seminal vesicle, Small intestine.
Medium only: breast cancer, liver cancer, prostate cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query for this target: (TITLE:"PML" OR ABSTRACT:"PML" OR TITLE:"PML nuclear body scaffold" OR ABSTRACT:"PML nuclear body scaffold" OR TITLE:"TRIM19" OR ABSTRACT:"TRIM19" OR TITLE:"RNF71" OR ABSTRACT:"RNF71") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PML, not a curated reading list.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Thyroid cancer, Leukaemia (all types), Skin cancer (all types).
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Skin cancer (all types), CIViC.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Skin cancer (all types), CIViC.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Skin cancer (all types), CIViC.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Skin cancer (all types), CIViC.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Skin cancer (all types), IntOGen.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Skin cancer (all types), Lung cancer (all types).
Shares Thyroid cancer, Skin cancer (all types), CIViC, IntOGen.