HAEM5:Acute promyelocytic leukaemia with PML::RARA fusion: Difference between revisions
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{{DISPLAYTITLE:Acute promyelocytic leukaemia with PML::RARA fusion}} | {{DISPLAYTITLE:Acute promyelocytic leukaemia with PML::RARA fusion}} | ||
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] | ||
{{Under Construction}} | {{Under Construction}} | ||
<blockquote class= | <blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Acute Promyelocytic Leukemia (APL) with PML-RARA]]. | ||
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|Subtype(s) | |Subtype(s) | ||
|Acute promyelocytic leukaemia with PML::RARA fusion | |Acute promyelocytic leukaemia with PML::RARA fusion | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
This AML subtype is classified based on the presence of a PML-RARA fusion, which results from fusion of the 5’ portion of PML at 15q24.1 and the 3’ portion of RARA at 17q21.1<ref>{{Cite journal|last=de Thé|first=H.|last2=Chomienne|first2=C.|last3=Lanotte|first3=M.|last4=Degos|first4=L.|last5=Dejean|first5=A.|date=1990|title=The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus|url=https://www.ncbi.nlm.nih.gov/pubmed/2170850|journal=Nature|volume=347|issue=6293|pages=558–561|doi=10.1038/347558a0|issn=0028-0836|pmid=2170850}}</ref>. 5'PML-3'RARA transcript is expressed in all cases, and 5'RARA-3'PML transcript is found in 2/3 of cases<ref>{{Cite journal|last=Warrell|first=R. P.|last2=de Thé|first2=H.|last3=Wang|first3=Z. Y.|last4=Degos|first4=L.|date=1993|title=Acute promyelocytic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/8515790|journal=The New England Journal of Medicine|volume=329|issue=3|pages=177–189|doi=10.1056/NEJM199307153290307|issn=0028-4793|pmid=8515790}}</ref>. Rare cases of APL have cryptic t(15;17)(q24.1;q21.1) such as submicroscopic insertion of RARA into PML leading to the expression of the PML-RARA transcript or three way translocations involving chromosomes 15 and 17 with an additional chromosome<ref name=":1">{{Cite journal|last=Grimwade|first=D.|last2=Gorman|first2=P.|last3=Duprez|first3=E.|last4=Howe|first4=K.|last5=Langabeer|first5=S.|last6=Oliver|first6=F.|last7=Walker|first7=H.|last8=Culligan|first8=D.|last9=Waters|first9=J.|date=1997|title=Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/9389704|journal=Blood|volume=90|issue=12|pages=4876–4885|issn=0006-4971|pmid=9389704}}</ref>. Several variant translocations involving RARA have also been identified, including t(11;17) and t(5;17)<ref name=":1" />. The 4th edition revision to the World Health Organization renamed APL with t(15;17)(q24.1;q21.1) as APL with PML-RARA<ref name=":0" /><ref>{{Cite journal|last=Arber|first=Daniel A.|last2=Orazi|first2=Attilio|last3=Hasserjian|first3=Robert|last4=Thiele|first4=Jürgen|last5=Borowitz|first5=Michael J.|last6=Le Beau|first6=Michelle M.|last7=Bloomfield|first7=Clara D.|last8=Cazzola|first8=Mario|last9=Vardiman|first9=James W.|date=2016|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/27069254|journal=Blood|volume=127|issue=20|pages=2391–2405|doi=10.1182/blood-2016-03-643544|issn=1528-0020|pmid=27069254}}</ref>. | This AML subtype is classified based on the presence of a PML-RARA fusion, which results from fusion of the 5’ portion of PML at 15q24.1 and the 3’ portion of RARA at 17q21.1<ref>{{Cite journal|last=de Thé|first=H.|last2=Chomienne|first2=C.|last3=Lanotte|first3=M.|last4=Degos|first4=L.|last5=Dejean|first5=A.|date=1990|title=The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus|url=https://www.ncbi.nlm.nih.gov/pubmed/2170850|journal=Nature|volume=347|issue=6293|pages=558–561|doi=10.1038/347558a0|issn=0028-0836|pmid=2170850}}</ref>. 5'PML-3'RARA transcript is expressed in all cases, and 5'RARA-3'PML transcript is found in 2/3 of cases<ref>{{Cite journal|last=Warrell|first=R. P.|last2=de Thé|first2=H.|last3=Wang|first3=Z. Y.|last4=Degos|first4=L.|date=1993|title=Acute promyelocytic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/8515790|journal=The New England Journal of Medicine|volume=329|issue=3|pages=177–189|doi=10.1056/NEJM199307153290307|issn=0028-4793|pmid=8515790}}</ref>. Rare cases of APL have cryptic t(15;17)(q24.1;q21.1) such as submicroscopic insertion of RARA into PML leading to the expression of the PML-RARA transcript or three way translocations involving chromosomes 15 and 17 with an additional chromosome<ref name=":1">{{Cite journal|last=Grimwade|first=D.|last2=Gorman|first2=P.|last3=Duprez|first3=E.|last4=Howe|first4=K.|last5=Langabeer|first5=S.|last6=Oliver|first6=F.|last7=Walker|first7=H.|last8=Culligan|first8=D.|last9=Waters|first9=J.|date=1997|title=Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/9389704|journal=Blood|volume=90|issue=12|pages=4876–4885|issn=0006-4971|pmid=9389704}}</ref>. Several variant translocations involving RARA have also been identified, including t(11;17) and t(5;17)<ref name=":1" />. The 4th edition revision to the World Health Organization renamed APL with t(15;17)(q24.1;q21.1) as APL with PML-RARA<ref name=":0">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.</ref><ref>{{Cite journal|last=Arber|first=Daniel A.|last2=Orazi|first2=Attilio|last3=Hasserjian|first3=Robert|last4=Thiele|first4=Jürgen|last5=Borowitz|first5=Michael J.|last6=Le Beau|first6=Michelle M.|last7=Bloomfield|first7=Clara D.|last8=Cazzola|first8=Mario|last9=Vardiman|first9=James W.|date=2016|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/27069254|journal=Blood|volume=127|issue=20|pages=2391–2405|doi=10.1182/blood-2016-03-643544|issn=1528-0020|pmid=27069254}}</ref>. | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in: | ||
* Chromosomal Rearrangements (Gene Fusions) | * Chromosomal Rearrangements (Gene Fusions) | ||
* Individual Region Genomic Gain/Loss/LOH | * Individual Region Genomic Gain/Loss/LOH | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
Not applicable | Not applicable | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
Not applicable | Not applicable | ||
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | ||
<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
There is not specific information on mutations related to this subtype of AML at this time. | There is not specific information on mutations related to this subtype of AML at this time. | ||
===Other Mutations=== | ===Other Mutations=== | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
The protein encoded by the PML (promyelocytic leukemia) gene is a member of the tripartite motif (TRIM) family and it functions as a transcription factor and tumor suppressor. PML is the core component of subnuclear structures called PML nuclear bodies (PML-NBs) and it interacts with a large number of proteins including p53 and has been implicated in several cellular functions such as cellular senescence, apoptosis, and hematopoietic stem cell maintenance<ref>{{Cite journal|last=Pearson|first=M.|last2=Carbone|first2=R.|last3=Sebastiani|first3=C.|last4=Cioce|first4=M.|last5=Fagioli|first5=M.|last6=Saito|first6=S.|last7=Higashimoto|first7=Y.|last8=Appella|first8=E.|last9=Minucci|first9=S.|date=2000|title=PML regulates p53 acetylation and premature senescence induced by oncogenic Ras|url=https://www.ncbi.nlm.nih.gov/pubmed/10910364|journal=Nature|volume=406|issue=6792|pages=207–210|doi=10.1038/35018127|issn=0028-0836|pmid=10910364}}</ref><ref>{{Cite journal|last=Bernardi|first=Rosa|last2=Pandolfi|first2=Pier Paolo|date=2007|title=Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies|url=https://www.ncbi.nlm.nih.gov/pubmed/17928811|journal=Nature Reviews. Molecular Cell Biology|volume=8|issue=12|pages=1006–1016|doi=10.1038/nrm2277|issn=1471-0080|pmid=17928811}}</ref>. The gene RARA (Retinoic acid receptor, alpha) encodes a nuclear retinoic acid receptor which regulates transcription in a ligand-dependent manner<ref>{{Cite journal|last=Melnick|first=A.|last2=Licht|first2=J. D.|date=1999|title=Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/10233871|journal=Blood|volume=93|issue=10|pages=3167–3215|issn=0006-4971|pmid=10233871}}</ref>. The fusion of PML and RARA results in expression of a hybrid protein with altered functions. This fusion protein deregulates transcriptional control such as RAR targets and disrupts PML nuclear bodies<ref>{{Cite journal|last=de Thé|first=Hugues|last2=Chen|first2=Zhu|date=2010|title=Acute promyelocytic leukaemia: novel insights into the mechanisms of cure|url=https://www.ncbi.nlm.nih.gov/pubmed/20966922|journal=Nature Reviews. Cancer|volume=10|issue=11|pages=775–783|doi=10.1038/nrc2943|issn=1474-1768|pmid=20966922}}</ref>. | The protein encoded by the PML (promyelocytic leukemia) gene is a member of the tripartite motif (TRIM) family and it functions as a transcription factor and tumor suppressor. PML is the core component of subnuclear structures called PML nuclear bodies (PML-NBs) and it interacts with a large number of proteins including p53 and has been implicated in several cellular functions such as cellular senescence, apoptosis, and hematopoietic stem cell maintenance<ref>{{Cite journal|last=Pearson|first=M.|last2=Carbone|first2=R.|last3=Sebastiani|first3=C.|last4=Cioce|first4=M.|last5=Fagioli|first5=M.|last6=Saito|first6=S.|last7=Higashimoto|first7=Y.|last8=Appella|first8=E.|last9=Minucci|first9=S.|date=2000|title=PML regulates p53 acetylation and premature senescence induced by oncogenic Ras|url=https://www.ncbi.nlm.nih.gov/pubmed/10910364|journal=Nature|volume=406|issue=6792|pages=207–210|doi=10.1038/35018127|issn=0028-0836|pmid=10910364}}</ref><ref>{{Cite journal|last=Bernardi|first=Rosa|last2=Pandolfi|first2=Pier Paolo|date=2007|title=Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies|url=https://www.ncbi.nlm.nih.gov/pubmed/17928811|journal=Nature Reviews. Molecular Cell Biology|volume=8|issue=12|pages=1006–1016|doi=10.1038/nrm2277|issn=1471-0080|pmid=17928811}}</ref>. The gene RARA (Retinoic acid receptor, alpha) encodes a nuclear retinoic acid receptor which regulates transcription in a ligand-dependent manner<ref>{{Cite journal|last=Melnick|first=A.|last2=Licht|first2=J. D.|date=1999|title=Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/10233871|journal=Blood|volume=93|issue=10|pages=3167–3215|issn=0006-4971|pmid=10233871}}</ref>. The fusion of PML and RARA results in expression of a hybrid protein with altered functions. This fusion protein deregulates transcriptional control such as RAR targets and disrupts PML nuclear bodies<ref>{{Cite journal|last=de Thé|first=Hugues|last2=Chen|first2=Zhu|date=2010|title=Acute promyelocytic leukaemia: novel insights into the mechanisms of cure|url=https://www.ncbi.nlm.nih.gov/pubmed/20966922|journal=Nature Reviews. Cancer|volume=10|issue=11|pages=775–783|doi=10.1038/nrc2943|issn=1474-1768|pmid=20966922}}</ref>. | ||
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(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references /> | (use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references /> | ||
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==Notes== | ==Notes== | ||
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<nowiki>*</nowiki>''Citation of this Page'': “Acute promyelocytic leukaemia with PML::RARA fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_promyelocytic_leukaemia_with_PML::RARA_fusion</nowiki>. | <nowiki>*</nowiki>''Citation of this Page'': “Acute promyelocytic leukaemia with PML::RARA fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_promyelocytic_leukaemia_with_PML::RARA_fusion</nowiki>. | ||
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]] | [[Category:HAEM5]] | ||
[[Category:DISEASE]] | |||
[[Category:Diseases A]] | |||