HAEM5:Acute myeloid leukaemia with KMT2A rearrangement: Difference between revisions
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<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 Myeloid Leukemia (AML) with t(9;11)(p21.3;q23.3); KMT2A-MLLT3]]. | ||
}}</blockquote> | }}</blockquote> | ||
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Megan Piazza, Ph.D., Yiming Zhong, Ph.D., Shashi Shetty, Ph.D. | Megan Piazza, Ph.D., Yiming Zhong, Ph.D., Shashi Shetty, Ph.D. | ||
==WHO Classification of Disease== | ==WHO Classification of Disease== | ||
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|} | |} | ||
== | ==Related Terminology== | ||
{| class="wikitable" | {| class="wikitable" | ||
|+ | |+ | ||
|Acceptable | |Acceptable | ||
| | |Acute myeloid leukaemia with KMT2A::MLLT3 or other exact fusion; acute myeloid leukaemia with t(9;11)(p21.3;q23.3) or other exact balanced translocation | ||
|- | |- | ||
|Not Recommended | |Not Recommended | ||
| | |Acute myeloid leukaemia with MLL rearrangement | ||
|} | |} | ||
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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 translocation between chromosomes 9 and 11, specifically t(9;11)(p21.3;q23.3). This translocation leads to the fusion of the 5’ portion of ''KMT2A'' at 11q23.3 and the 3’ portion of ''MLLT3'' at 9p21.3. Both reciprocal fusions are expressed, however, the KMT2A-MLLT3 fusion on the derivative chromosome 11 is the candidate oncoprotein as it contains the putative functional domains of both proteins<ref name=":0" /><ref name=":1" /><ref name=":3">{{Cite journal|last=Mrózek|first=K.|last2=Heinonen|first2=K.|last3=Lawrence|first3=D.|last4=Carroll|first4=A. J.|last5=Koduru|first5=P. R.|last6=Rao|first6=K. W.|last7=Strout|first7=M. P.|last8=Hutchison|first8=R. E.|last9=Moore|first9=J. O.|date=1997|title=Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study|url=https://www.ncbi.nlm.nih.gov/pubmed/9373264|journal=Blood|volume=90|issue=11|pages=4532–4538|issn=0006-4971|pmid=9373264}}</ref>. | This AML subtype is classified based on the translocation between chromosomes 9 and 11, specifically t(9;11)(p21.3;q23.3). This translocation leads to the fusion of the 5’ portion of ''KMT2A'' at 11q23.3 and the 3’ portion of ''MLLT3'' at 9p21.3. Both reciprocal fusions are expressed, however, the KMT2A-MLLT3 fusion on the derivative chromosome 11 is the candidate oncoprotein as it contains the putative functional domains of both proteins<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, 136-138.</ref><ref name=":1">{{Cite journal|last=Byrd|first=John C.|last2=Mrózek|first2=Krzysztof|last3=Dodge|first3=Richard K.|last4=Carroll|first4=Andrew J.|last5=Edwards|first5=Colin G.|last6=Arthur|first6=Diane C.|last7=Pettenati|first7=Mark J.|last8=Patil|first8=Shivanand R.|last9=Rao|first9=Kathleen W.|date=2002|title=Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461)|url=https://www.ncbi.nlm.nih.gov/pubmed/12393746|journal=Blood|volume=100|issue=13|pages=4325–4336|doi=10.1182/blood-2002-03-0772|issn=0006-4971|pmid=12393746}}</ref><ref name=":3">{{Cite journal|last=Mrózek|first=K.|last2=Heinonen|first2=K.|last3=Lawrence|first3=D.|last4=Carroll|first4=A. J.|last5=Koduru|first5=P. R.|last6=Rao|first6=K. W.|last7=Strout|first7=M. P.|last8=Hutchison|first8=R. E.|last9=Moore|first9=J. O.|date=1997|title=Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study|url=https://www.ncbi.nlm.nih.gov/pubmed/9373264|journal=Blood|volume=90|issue=11|pages=4532–4538|issn=0006-4971|pmid=9373264}}</ref>. | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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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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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Chr #!! | !Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s) | ||
! | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | ||
! | !Established Clinical Significance Per Guidelines - Yes or No (Source) | ||
! | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span> | |<span class="blue-text">EXAMPLE:</span> | ||
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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> | ||
The t(9;11)( p21.3;q23.3) can present with secondary abnormalities, most frequently trisomy of chromosome 8<ref name=":1" /><ref name=":3" />. | The t(9;11)( p21.3;q23.3) can present with secondary abnormalities, most frequently trisomy of chromosome 8<ref name=":1" /><ref name=":3" />. | ||
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!Chromosomal Pattern | !Chromosomal Pattern | ||
!Molecular Pathogenesis | !Molecular Pathogenesis | ||
! | !Prevalence - | ||
Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
! | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | ||
! | !Established Clinical Significance Per Guidelines - Yes or No (Source) | ||
! | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span> | |<span class="blue-text">EXAMPLE:</span> | ||
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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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{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene!! | !Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence - | ||
Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
! | !Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | ||
! | !Established Clinical Significance Per Guidelines - Yes or No (Source) | ||
! | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
|<span class="blue-text">EXAMPLE:</span>''EGFR'' | |<span class="blue-text">EXAMPLE:</span>''EGFR'' | ||
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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> | ||
NA | NA | ||
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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 ''KMT2A'' (Lysine Methyltransferase 2A) gene encodes a protein that complexes with other proteins and functions to regulate gene transcription through chromatin remodeling. This protein plays a vital role in regulating gene expressing during early development and hematopoiesis. The ''MLLT3'' (Super Elongation Complex Subunit) gene encodes a protein that is an element of the super elongation complex (SEC). The SEC is a complex that plays an essential role in regulating the activity of RNA polymerase II transcription. The fusion protein created, KMT2A-MLLT3, leads to the promotion of transcriptional elongation, activation of genes that would typically be silenced, and thus inhibits hematopoietic cells from properly maturing<ref>{{Cite journal|last=Mueller|first=Dorothee|last2=García-Cuéllar|first2=María-Paz|last3=Bach|first3=Christian|last4=Buhl|first4=Sebastian|last5=Maethner|first5=Emanuel|last6=Slany|first6=Robert K.|date=2009|title=Misguided transcriptional elongation causes mixed lineage leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/19956800|journal=PLoS biology|volume=7|issue=11|pages=e1000249|doi=10.1371/journal.pbio.1000249|issn=1545-7885|pmc=2774266|pmid=19956800}}</ref>. | The ''KMT2A'' (Lysine Methyltransferase 2A) gene encodes a protein that complexes with other proteins and functions to regulate gene transcription through chromatin remodeling. This protein plays a vital role in regulating gene expressing during early development and hematopoiesis. The ''MLLT3'' (Super Elongation Complex Subunit) gene encodes a protein that is an element of the super elongation complex (SEC). The SEC is a complex that plays an essential role in regulating the activity of RNA polymerase II transcription. The fusion protein created, KMT2A-MLLT3, leads to the promotion of transcriptional elongation, activation of genes that would typically be silenced, and thus inhibits hematopoietic cells from properly maturing<ref>{{Cite journal|last=Mueller|first=Dorothee|last2=García-Cuéllar|first2=María-Paz|last3=Bach|first3=Christian|last4=Buhl|first4=Sebastian|last5=Maethner|first5=Emanuel|last6=Slany|first6=Robert K.|date=2009|title=Misguided transcriptional elongation causes mixed lineage leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/19956800|journal=PLoS biology|volume=7|issue=11|pages=e1000249|doi=10.1371/journal.pbio.1000249|issn=1545-7885|pmc=2774266|pmid=19956800}}</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 myeloid leukaemia with KMT2A rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_KMT2A_rearrangement</nowiki>. | <nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with KMT2A rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_KMT2A_rearrangement</nowiki>. | ||
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]] | [[Category:HAEM5]] | ||
[[Category:DISEASE]] | |||
[[Category:Diseases A]] | |||