HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion: Difference between revisions

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{{DISPLAYTITLE:Acute myeloid leukaemia with RBM15::MRTFA fusion}}
{{DISPLAYTITLE:Acute myeloid leukaemia with RBM15::MRTFA 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='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) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1]].
<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) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1]].
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|Subtype(s)
|Subtype(s)
|Acute myeloid leukaemia with RBM15::MRTFA fusion
|Acute myeloid leukaemia with RBM15::MRTFA fusion
|}
==Definition / Description of Disease==
This is a distinct entity in the World Health Organization (WHO) classification system<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, p139-140.</ref>.
==Synonyms / Terminology==
None.
==Epidemiology / Prevalence==
Accounts for <1% of AML, has a female predominance, can be congenital, and is restricted to infants and children below the age of 3 years (median onset of 4 months), most of whom do not have Down syndrome<ref name=":0" />.
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
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Usually presents with marked organomegaly, especially hepatosplenomegaly, anemia, thrombocytopenia and a moderately elevated white blood cell count<ref name=":0" />.
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<center><span style="color:Maroon">'''End of V4 Section'''</span>
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==Sites of Involvement==
Blood, bone marrow
==Morphologic Features==
This AML subtype generally has megakaryocyte lineage maturation in a normocellular to hypercellular marrow, often with reticulin and collagenous fibrosis<ref name=":0" />.  The blasts are similar to those of acute megakaryoblastic leukemia.  Small and large megakaryoblasts can be present and some cases have admixture with more morphologically undifferentiated blasts that have a high nuclear-cytoplasmic ratio (resemble lymphoblasts).  The megakaryoblasts are usually medium to large (12-18 μm), have a slightly irregular or indented and round nucleus with fine reticular chromatin, one to three nucleoli, basophilic and often agranular cytoplasm, and may have distinct blebs or pseudopod formation.  Micromegakaryocytes are common, dysplastic features of granulocytic and erythroid cells are not typically present, and some cases have a stromal pattern of bone marrow infiltration that mimics a metastatic tumor<ref name=":0" />.
It may be difficult to identify the minimum diagnostic criteria of 20% blasts in an aspirate in cases involving a fibrotic marrow.  Correlation with bone marrow biopsy results is important in such cases<ref name=":0" />.
==Immunophenotype==
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD36, CD41 (glycoprotein IIb/IIIa) and/or CD61 (glycoprotein IIIa) and/or less frequently CD42b (glycoprotein Ib)
|-
|Positive (subset)||CD13, CD33
|-
|Negative (universal)||Sudan Black B (SBB) and Myeloperoxidase (MPO), Terminal Deoxynucleotidyl Transferase (TdT), lymphoid markers
|-
|Negative (subset)||CD34, CD45, HLA-DR
|}
|}


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This AML subtype is classified based on the presence of a t(1;22)(p13.3;q13.1), which results in fusion of ''RBM15''(''OTT'') at 1p13.3 [hg38] and ''MKL1''(''MAL'') at 22q13.1 [hg38] with variable breakpoints<ref name=":1">{{Cite journal|last=Ma|first=Z.|last2=Morris|first2=S. W.|last3=Valentine|first3=V.|last4=Li|first4=M.|last5=Herbrick|first5=J. A.|last6=Cui|first6=X.|last7=Bouman|first7=D.|last8=Li|first8=Y.|last9=Mehta|first9=P. K.|date=2001|title=Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/11431691|journal=Nature Genetics|volume=28|issue=3|pages=220–221|doi=10.1038/90054|issn=1061-4036|pmid=11431691}}</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>.  Although both reciprocal fusions are expressed, the ''RBM15''-''MKL1'' fusion on the derivative chromosome 22 is the candidate oncoprotein because it contains all of the putative functional domains of both proteins<ref name=":1" />. Typically the ''RBM15''-''MKL1'' fusion presents as the sole abnormality<ref name=":0" />.
This AML subtype is classified based on the presence of a t(1;22)(p13.3;q13.1), which results in fusion of ''RBM15''(''OTT'') at 1p13.3 [hg38] and ''MKL1''(''MAL'') at 22q13.1 [hg38] with variable breakpoints<ref name=":1">{{Cite journal|last=Ma|first=Z.|last2=Morris|first2=S. W.|last3=Valentine|first3=V.|last4=Li|first4=M.|last5=Herbrick|first5=J. A.|last6=Cui|first6=X.|last7=Bouman|first7=D.|last8=Li|first8=Y.|last9=Mehta|first9=P. K.|date=2001|title=Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/11431691|journal=Nature Genetics|volume=28|issue=3|pages=220–221|doi=10.1038/90054|issn=1061-4036|pmid=11431691}}</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>.  Although both reciprocal fusions are expressed, the ''RBM15''-''MKL1'' fusion on the derivative chromosome 22 is the candidate oncoprotein because it contains all of the putative functional domains of both proteins<ref name=":1" />. Typically the ''RBM15''-''MKL1'' fusion presents as the sole abnormality<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, p139-140.</ref>.


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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<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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Not applicable
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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.


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COSMIC does not have specific information on mutations related to this subtype of AML.
COSMIC does not have specific information on mutations related to this subtype of AML.
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The molecular mechanism is not completely understand, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways<ref name=":0" /><ref name=":1" />.
The molecular mechanism is not completely understand, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways<ref name=":0" /><ref name=":1" />.
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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 RBM15::MRTFA fusion”. 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_RBM15::MRTFA_fusion</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with RBM15::MRTFA fusion”. 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_RBM15::MRTFA_fusion</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases A]]