Difference between revisions of "PML"

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(Created page with "==Primary Author(s)*== Put your text here __TOC__ ==Synonyms== Put your text here EXAMPLE: Tumor protein p53, ''LFS1, p53, BCC7, TRP53'' ==Genomic Location== '''Cytoban...")
 
 
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==Primary Author(s)*==
 
==Primary Author(s)*==
 
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Brian Davis PhD
Put your text here
 
  
 
__TOC__
 
__TOC__
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==Synonyms==
 
==Synonyms==
  
Put your text here
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"Promyelocytic Leukemia"; "Tripartite Motif-Containing Protein 19"; TRIM19; "RING Finger Protein 71"; RNF71; MYL
 
 
EXAMPLE: Tumor protein p53, ''LFS1, p53, BCC7, TRP53''
 
  
 
==Genomic Location==
 
==Genomic Location==
  
'''Cytoband:''' Put your text here. EXAMPLE: 17p13.1
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'''Cytoband:''' 15q24.1
  
 
'''Genomic Coordinates:'''  
 
'''Genomic Coordinates:'''  
  
Put your text here
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chr15:74,287,014-74,340,160(GRCh37/hg19)
 +
 
 +
chr15:73,994,673-74,047,819(GRCh38/hg38)
  
EXAMPLE: chr17:7,571,720-7,590,868 [hg19]
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==Cancer Category/Type==
  
EXAMPLE: chr17:7,668,402-7,687,538 [hg38]
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[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
  
==Cancer Category/Type==
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---[http://www.ccga.io/index.php/HAEM5:Acute_promyelocytic_leukaemia_with_PML::RARA_fusion Acute Promyelocytic Leukemia (APL) with PML-RARA]
  
Put your text here
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Based on the early French-American-British (FAB) classification, Acute Promyelocytic Leukaemia (APL) is one of the subtypes (M3) of Acute Myeloid Leukemia AML [1].  The PML-RARA fusion is reportedly found in 5-15% of AML and occurs at any age but predominantly in adults in mid-life [1,2].  ''RARA'' fusion proteins behave as potent transcriptional repressors of retinoic acid signaling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of all-trans retinoic acid (ATRA) or arsenic trioxide [1-5].  ATO (arsenic trioxide) also induces differentiation of the malignant myeloid clone by dissociating the PML/RAR-alpha-RXR complex from the target genes and was found to have a synergistic action with ATRA [5].
  
 
==Gene Overview==
 
==Gene Overview==
  
Put your text here.
+
The ''PML'' gene encodes a protein which functions via its association with nuclear bodies (NBs) in a wide range of important cellular processes including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. The protein acts as the scaffold for NBs, allowing other proteins to shuttle in and out.  Some of the Pml proteins diverse actions include: activating ''RB1'', inhibiting ''AKT1'', negatively affecings the PI3K pathway by inhibiting MTOR and activating ''PTEN'', and positively regulates p53/''TP53''.
 +
 
 +
Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) that is almost entirely caused by the t(15;17)q22;q11) resulting in the PML-RARA fusion gene.  Unlike the normal retinoic acid receptor, the Pml-Rara protein does not respond to the ligand signal to induce transcription of genes, so the genes remain repressed, ultimately resulting in the inhibition of gene expression for hematopoietic differentiation and the maturation arrest of hematopoietic progenitors at the promyelocyte stage.  In addition, while the normal PML protein blocks proliferation and induces apoptosis in combination with other proteins, the Pml-Rara protein acts as a dominant repressor of the normal PML protein [4].
  
 
==Common Alteration Types==
 
==Common Alteration Types==
  
Put your text here and/or fill in the table with an X where applicable
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The translocation involving ''PML'' and ''RARA'' is found in more than 90% of APL cases.
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 39: Line 40:
 
! Copy Number Loss  !! Copy Number Gain  !!  LOH  !!  Loss-of-Function Mutation  !!  Gain-of-Function Mutation  !!  Translocation/Fusion  
 
! Copy Number Loss  !! Copy Number Gain  !!  LOH  !!  Loss-of-Function Mutation  !!  Gain-of-Function Mutation  !!  Translocation/Fusion  
 
|-
 
|-
| EXAMPLE: X ||EXAMPLE: X || EXAMPLE: X  || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X
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| ||  ||   || || || X
 
|}
 
|}
  
 
==Internal Pages==
 
==Internal Pages==
  
Put your text here
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[http://www.ccga.io/index.php/HAEM5:Acute_promyelocytic_leukaemia_with_PML::RARA_fusion Acute Promyelocytic Leukemia (APL) with PML-RARA]
+
 
EXAMPLE [[Germline Cancer Predisposition Genes]]
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[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
 +
 
 +
[http://www.ccga.io/index.php/RARA RARA]
  
 
==External Links==
 
==External Links==
  
Put your text here - Include as applicable links to: 1) Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2) COSMIC, 3) CIViC, 4) St. Jude ProteinPaint, 5) Precision Medicine Knnowledgebase (Weill Cornell), 6) Cancer Index, 7) OncoKB, 8) My Cancer Genome, 9) UniProt, 10) Pfam, 11) GeneCards, 12) GeneReviews, and 13) Any gene-specific databases.
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'''[http://atlasgeneticsoncology.org/Genes/GC_PML.html ''PML'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
 +
 
 +
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=pml ''PML'' by COSMIC]''' - sequence information, expression, catalogue of mutations
 +
 
 +
'''[https://civicdb.org/events/genes/39/summary/variants/108/summary ''PML-RARA'' by CIViC]''' - general knowledge and evidence-based variant specific information
  
EXAMPLES
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'''[https://pecan.stjude.cloud/proteinpaint/pml ''PML'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.
  
'''[http://atlasgeneticsoncology.org/Genes/P53ID88.html ''TP53'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
+
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=pml ''PML'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
  
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TP53 ''TP53'' by COSMIC]''' - sequence information, expression, catalogue of mutations
+
'''[http://www.cancerindex.org/geneweb/PML.htm ''PML'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
  
'''[https://civicdb.org/events/genes/45/summary/variants/1300/summary ''TP53'' by CIViC]''' - general knowledge and evidence-based variant specific information
+
'''[https://www.mycancergenome.org/content/gene/pml/ ''PML'' by My Cancer Genome]''' - brief gene overview
  
'''[http://p53.iarc.fr/ ''TP53'' by IARC]''' - ''TP53'' database with reference sequences and mutational landscape
+
'''[http://www.uniprot.org/uniprot/P29590 ''PML'' by UniProt]''' - protein and molecular structure and function
  
'''[https://pecan.stjude.cloud/proteinpaint/tp53 ''TP53'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.
+
'''[http://pfam.xfam.org/protein/P29590 ''PML'' by Pfam]''' - gene and protein structure and function information
  
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=tp53 ''TP53'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
+
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=pml ''PML'' by GeneCards]''' - general gene information and summaries
  
'''[http://www.cancerindex.org/geneweb/TP53.htm ''TP53'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
+
'''[https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=5371 ''PML'' by NCBI Gene]''' - general gene information and summaries
  
'''[http://oncokb.org/#/gene/TP53 ''TP53'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
+
'''[http://www.omim.org/entry/102578 ''PML'' by OMIM]''' - compendium of human genes and genetic phenotypes
  
'''[https://www.mycancergenome.org/content/gene/tp53/ ''TP53'' by My Cancer Genome]''' - brief gene overview
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'''[https://databases.lovd.nl/shared/genes/PML ''PML'' by LOVD(3)]''' - Leiden Open Variation Database
  
'''[http://www.uniprot.org/uniprot/P04637 ''TP53'' by UniProt]''' - protein and molecular structure and function
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'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=PML ''PML'' by TICdb]''' - database of Translocation breakpoints In Cancer
  
'''[https://pfam.xfam.org/family/p53 ''TP53'' by Pfam]''' - gene and protein structure and function information
+
==References==
  
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=tp53 ''TP53'' by GeneCards]''' - general gene information and summaries
+
1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p134-136.  
  
'''[https://www.ncbi.nlm.nih.gov/books/NBK1311/ GeneReviews]''' - information on Li Fraumeni Syndrome
+
2. Hsu, K.S. and Kao, H.Y. (2018). PML: Regulation and multifaceted function beyond tumor suppression. Cell. Bioscience 8: 5, PMID 29416846. DOI: 10.1186/s13578-018-0204-8.
  
==References==
+
3. Cingam, S. R. and Koshy, N.V.  (2017).  Cancer, Leukemia, Promyelocytic, Acute (APL, APML).  https://www.ncbi.nlm.nih.gov/books/NBK459352/ Accessed August 3, 2018.
  
=== EXAMPLE Book ===
+
4. Schafer ES, et al., (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
#Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
 
  
=== EXAMPLE Journal Article ===
+
5. Ng CH and Chng WJ (2017). Recent advances in acute promyelocytic leukaemia. F1000Res 6:1273, PMID 28794865. DOI: 10.12688/f1000research.10736.1.
#Li Y, et al., (2001). Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 28:220-221, PMID 11431691.
 
  
 
== Notes ==
 
== Notes ==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 +
 +
[[Category:Cancer Genes P]]

Latest revision as of 14:45, 12 December 2023

Primary Author(s)*

Brian Davis PhD

Synonyms

"Promyelocytic Leukemia"; "Tripartite Motif-Containing Protein 19"; TRIM19; "RING Finger Protein 71"; RNF71; MYL

Genomic Location

Cytoband: 15q24.1

Genomic Coordinates:

chr15:74,287,014-74,340,160(GRCh37/hg19)

chr15:73,994,673-74,047,819(GRCh38/hg38)

Cancer Category/Type

Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms

---Acute Promyelocytic Leukemia (APL) with PML-RARA

Based on the early French-American-British (FAB) classification, Acute Promyelocytic Leukaemia (APL) is one of the subtypes (M3) of Acute Myeloid Leukemia AML [1]. The PML-RARA fusion is reportedly found in 5-15% of AML and occurs at any age but predominantly in adults in mid-life [1,2]. RARA fusion proteins behave as potent transcriptional repressors of retinoic acid signaling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of all-trans retinoic acid (ATRA) or arsenic trioxide [1-5]. ATO (arsenic trioxide) also induces differentiation of the malignant myeloid clone by dissociating the PML/RAR-alpha-RXR complex from the target genes and was found to have a synergistic action with ATRA [5].

Gene Overview

The PML gene encodes a protein which functions via its association with nuclear bodies (NBs) in a wide range of important cellular processes including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. The protein acts as the scaffold for NBs, allowing other proteins to shuttle in and out. Some of the Pml proteins diverse actions include: activating RB1, inhibiting AKT1, negatively affecings the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53.

Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) that is almost entirely caused by the t(15;17)q22;q11) resulting in the PML-RARA fusion gene. Unlike the normal retinoic acid receptor, the Pml-Rara protein does not respond to the ligand signal to induce transcription of genes, so the genes remain repressed, ultimately resulting in the inhibition of gene expression for hematopoietic differentiation and the maturation arrest of hematopoietic progenitors at the promyelocyte stage. In addition, while the normal PML protein blocks proliferation and induces apoptosis in combination with other proteins, the Pml-Rara protein acts as a dominant repressor of the normal PML protein [4].

Common Alteration Types

The translocation involving PML and RARA is found in more than 90% of APL cases.

Copy Number Loss Copy Number Gain LOH Loss-of-Function Mutation Gain-of-Function Mutation Translocation/Fusion
X

Internal Pages

Acute Promyelocytic Leukemia (APL) with PML-RARA

Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms

RARA

External Links

PML by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information

PML by COSMIC - sequence information, expression, catalogue of mutations

PML-RARA by CIViC - general knowledge and evidence-based variant specific information

PML by St. Jude ProteinPaint mutational landscape and matched expression data.

PML by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs

PML by Cancer Index - gene, pathway, publication information matched to cancer type

PML by My Cancer Genome - brief gene overview

PML by UniProt - protein and molecular structure and function

PML by Pfam - gene and protein structure and function information

PML by GeneCards - general gene information and summaries

PML by NCBI Gene - general gene information and summaries

PML by OMIM - compendium of human genes and genetic phenotypes

PML by LOVD(3) - Leiden Open Variation Database

PML by TICdb - database of Translocation breakpoints In Cancer

References

1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p134-136.

2. Hsu, K.S. and Kao, H.Y. (2018). PML: Regulation and multifaceted function beyond tumor suppression. Cell. Bioscience 8: 5, PMID 29416846. DOI: 10.1186/s13578-018-0204-8.

3. Cingam, S. R. and Koshy, N.V. (2017). Cancer, Leukemia, Promyelocytic, Acute (APL, APML). https://www.ncbi.nlm.nih.gov/books/NBK459352/ Accessed August 3, 2018.

4. Schafer ES, et al., (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.

5. Ng CH and Chng WJ (2017). Recent advances in acute promyelocytic leukaemia. F1000Res 6:1273, PMID 28794865. DOI: 10.12688/f1000research.10736.1.

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.